Rebuttal Letter to Reviewers: Complete Guide, Templates & Examples (2026)

Receiving peer review comments on your manuscript can trigger a range of emotions—from relief that your work wasn’t outright rejected to frustration at the extensive revisions requested. But here’s the reality: successfully responding to peer review comments through a well-crafted rebuttal letter is often the final hurdle between you and publication.

Studies show that manuscripts with thorough, professional response letters are significantly more likely to be accepted than those with defensive or incomplete responses. This guide will teach you how to write rebuttal letters that turn revision requests into acceptance, whether you’re agreeing with reviewers, respectfully disagreeing, or navigating impossible requests.

Whether you’ve received your first revision request or your tenth, writing a professional response letter (also called a rebuttal letter) is the final step between revision and acceptance. This comprehensive guide provides everything you need: proven templates, real examples, format guidelines, and strategic advice for every type of reviewer comment.

What you’ll get from this guide:

• ✅ 3 complete templates you can copy and adapt
• ✅ Real response examples for different scenarios (agreement, disagreement, impossible requests)
• ✅ Professional format guidelines with exact structure
• ✅ Tone and language that works with reviewers
• ✅ Common mistakes to avoid (that cause rejection)

Reading time: 18 minutes to read fully | 5 minutes to find what you need right now

Rebuttal Letter Checklist: Do You Have Everything?

Before you start writing, ensure you have:

Required Materials:

• [ ] Full reviewer comments and editor decision letter
• [ ] Your original manuscript (to reference what changed)
• [ ] Revised manuscript with track changes enabled
• [ ] Co-author input on how to address major concerns

Structure Requirements:

• [ ] Opening greeting thanking editor and reviewers
• [ ] Executive summary (3-5 major changes)
• [ ] Response to EVERY reviewer comment (no exceptions)
• [ ] Specific page/line numbers for all changes
• [ ] Professional, non-defensive tone throughout
• [ ] Closing with contact information

Format Requirements:

• [ ] Clear separation between reviewers
• [ ] Numbered comments (1.1, 1.2, 2.1, 2.2)
• [ ] Reviewer comments distinguished (bold/italics)
• [ ] Your responses in regular text
• [ ] Both marked and clean manuscript versions

Quality Checks:

• [ ] Zero typos or grammatical errors
• [ ] All page/line numbers verified as accurate
• [ ] Co-authors have reviewed and approved
• [ ] Every single comment addressed (including minor ones)

Time estimate: 4-8 hours for minor revision | 10-20 hours for major revision

In this guide:

What Is a Rebuttal Letter in an Academic Journal?

A rebuttal letter (also called a response letter, revision letter, or point-by-point response) is a formal document you submit alongside your revised manuscript that addresses every comment made by peer reviewers and the editor. It demonstrates how you’ve incorporated feedback, explains your reasoning for any changes you didn’t make, and documents all modifications to your manuscript.

Three Critical Functions

1. Documentation: Your rebuttal letter creates a record of how you addressed each concern, making it easy for editors and reviewers to verify that you’ve been thorough.

2. Persuasion: When you disagree with a reviewer or can’t implement a suggestion, your rebuttal letter makes the case for why your approach is scientifically sound.

3. Professionalism: A well-written response letter signals that you’re a careful, thoughtful researcher who takes peer review seriously—qualities that increase editors’ confidence in accepting your work.

When You Need a Rebuttal Letter

You’ll need to write a response letter whenever you receive any of these journal decision statuses:

• Major Revision: Substantial changes required, often involving new analyses or experiments
• Minor Revision: Smaller changes to text, figures, or organization
• Revise and Resubmit: Significant concerns that require resubmission for another full review
• Conditional Accept: Final minor tweaks before acceptance

Even if you disagree fundamentally with reviewer comments, never simply ignore them. Editors expect a response to every point raised, and failing to address comments almost guarantees rejection.

Rebuttal Letter vs. Response Letter: What’s the Difference?

Nothing—they’re the same document with different names. “Rebuttal letter” sounds more formal and implies you’re defending your work, while “response letter” sounds more collaborative. Both terms refer to the point-by-point document addressing reviewer feedback.

Some journals use “rebuttal” when authors are disagreeing with comments, and “response” for more straightforward revisions, but this isn’t a universal distinction. Use whichever term your target journal uses in their instructions to authors.

Essential Components of Every Rebuttal Letter

Regardless of how you organize your response, these elements must be present:

1. Opening: Professional Greeting and Thanks

Start by thanking the editor and reviewers for their time and constructive feedback. This isn’t just politeness—it sets a collaborative tone that makes editors and reviewers more receptive to your responses, especially if you’ll be disagreeing with some comments.

Example:

Dear Dr. Martinez,

Thank you for the opportunity to revise our manuscript titled "CRISPR-Mediated Targeting of Oncogenic KRAS Mutations" (Manuscript ID: JMB-2025-1234). We sincerely appreciate the thoughtful and constructive feedback from both reviewers. Their insights have strengthened our manuscript considerably, and we believe the revised version addresses all concerns raised.

Below we provide detailed point-by-point responses to each comment, with specific page and line number references to changes in the revised manuscript.

2. Executive Summary of Major Changes

Immediately after your greeting, provide a brief overview (3-5 sentences) of the most significant revisions you made. This helps busy editors quickly assess whether you’ve addressed the big issues before diving into details.

Example:

SUMMARY OF MAJOR REVISIONS:

The most significant changes to our manuscript include:
1. Addition of new in vivo efficacy data using patient-derived xenograft models (Figure 4, pages 14-16)
2. Expanded discussion of off-target effects with new bioinformatics analysis (pages 19-20, lines 378-425)
3. Reorganization of the Methods section for improved clarity (pages 7-10)
4. Addition of eight new references as suggested by reviewers
5. Revision of statistical analyses to include additional controls (Table 2, Supplementary Table S3)

All changes are highlighted in yellow in the marked-up manuscript version.

3. Point-by-Point Responses

This is the heart of your rebuttal letter. For each reviewer comment, follow this structure:

Comment: [Copy the exact reviewer comment or provide enough context] Response: [Your detailed response] Changes made: [Specific manuscript locations]

Organize responses by reviewer (Reviewer 1, Reviewer 2, Editor) with clear numbering or labeling for each comment.

4. Closing: Appreciation and Contact Information

End by reiterating your thanks, expressing confidence that the revisions address concerns, and providing your contact information for follow-up questions.

Example:

We believe these revisions have substantially strengthened our manuscript and fully address the concerns raised by both reviewers. We are grateful for the opportunity to improve our work through this process. 

Should you or the reviewers require any clarification or additional information, please don't hesitate to contact me.

Sincerely,

Dr. James Chen
Corresponding Author
Department of Molecular Oncology
Massachusetts Institute of Technology
Email: jchen@mit.edu
Phone: +1-617-555-0123
ORCID: 0000-0002-1234-5678

Structure and Formatting Best Practices

A well-structured rebuttal letter makes reviewing your revisions faster and easier, which directly impacts your chances of acceptance.

Professional Formatting

Use this format for maximum clarity:

Page Header: "Response to Reviewers - Manuscript JMB-2025-1234" | Author et al.

Dear Dr. [Editor],

[Opening paragraph with thanks and summary]

SUMMARY OF MAJOR CHANGES:
[Bullet list of 3-5 major revisions]

──────────────────────────────────────────────────

REVIEWER 1

Comment 1.1: [Reviewer's comment in italics or bold]

Response: [Your response in regular text]

Changes made: Section 2.3, pages 8-9, lines 145-178; Figure 3 caption, page 15.

Comment 1.2: [Next comment]

Response: [Your response]

Changes made: [Locations]

──────────────────────────────────────────────────

REVIEWER 2

Comment 2.1: [Reviewer's comment]

Response: [Your response]

Changes made: [Locations]

──────────────────────────────────────────────────

[Closing paragraph]

Sincerely,
[All authors listed]

Formatting Tips That Improve Clarity

Distinguish reviewer comments from your responses:

• Bold or italicize all reviewer comments
• Use regular text for your responses
• Consider colored text (reviewer comments in blue, your responses in black)

Number everything systematically:

• Use format like “Comment 1.1, 1.2” for Reviewer 1
• Use “Comment 2.1, 2.2” for Reviewer 2
• Use “Comment E.1” for editor comments

Include precise locations:

• Always cite page numbers
• Include line numbers if your journal uses them
• Reference specific sections, figures, or tables
• Example: “Section 3.2, page 12, lines 245-267, and Supplementary Figure S2”

Highlight changes in your manuscript:

• Use Word’s Track Changes or yellow highlighting
• Note at the top of your response letter: “All changes are highlighted in yellow in the marked-up manuscript version”
• Some journals prefer separate “clean” and “marked” versions—check guidelines

Use white space effectively:

• Add horizontal lines between reviewers
• Use extra line breaks between comments
• Don’t cram everything together—readability matters

How to Address Different Types of Comments

Not all reviewer comments are created equal. Here’s how to handle five common types you’ll encounter.

Type 1: Agreement (The Easy Ones)

When you agree with a comment, acknowledge it graciously and specify exactly what you changed.

Reviewer Comment: “The methodology section lacks sufficient detail about the CRISPR delivery system. Readers will need more information to replicate this work.”

Your Response:

Response: We agree completely and have substantially expanded the methodology section. We now include:
- Detailed composition of the lipid nanoparticle formulation (Section 2.3, page 8, lines 156-178)
- Step-by-step protocol for nanoparticle preparation (Supplementary Methods, pages S3-S4)
- Characterization data for particle size and zeta potential (new Supplementary Table S1)
- Specific transfection conditions and timelines (Section 2.3, page 9, lines 185-201)

We thank the reviewer for identifying this gap, which has significantly improved the reproducibility of our methods.

Changes made: Section 2.3, pages 8-9, lines 156-201; Supplementary Methods pages S3-S4; new Supplementary Table S1.

Key Elements:

• Explicit agreement
• Specific description of what you added
• Precise locations
• Brief acknowledgment of the improvement
• Professional tone

Type 2: Clarification Needed (Fixing Confusion)

When reviewers are confused or missed something in your original manuscript, don’t be defensive. Instead, clarify in both your response AND improve your manuscript so future readers won’t be confused.

Reviewer Comment: “The statistical analysis is unclear. Did the authors use a one-tailed or two-tailed test? What was the significance threshold?”

Your Response:

Response: We apologize for the lack of clarity. We used two-tailed Student's t-tests throughout, with a significance threshold of p<0.05 (Bonferroni-corrected for multiple comparisons). While this was mentioned briefly in the original Methods section, we recognize it was not sufficiently prominent.

We have now:
1. Added a dedicated "Statistical Analysis" subsection clearly stating all test types, significance thresholds, and correction methods (Section 2.7, page 11, lines 234-256)
2. Included statistical details in figure legends (e.g., Figure 2 legend now states: "Data analyzed by two-tailed Student's t-test, **p<0.01, ***p<0.001")
3. Added a statement about sample size determination and power analysis (Section 2.7, page 11, lines 249-253)

We believe these additions eliminate ambiguity and make our statistical approach transparent.

Changes made: New Section 2.7 "Statistical Analysis," page 11, lines 234-256; updated figure legends for Figures 2-5; new Supplementary Table S2 showing all statistical tests used.

Key Elements:

• No defensiveness (“The reviewer clearly didn’t read carefully…”)
• Acknowledgment that clarity was insufficient
• Comprehensive fix that prevents future confusion
• Improved manuscript, not just a response explanation
• Professional problem-solving approach

Type 3: Disagreement (The Tricky Ones)

Disagreeing with reviewers requires careful diplomacy and strong evidence. You need to maintain your scientific integrity while showing respect for their expertise. Learn more strategies for alternatives to “we respectfully disagree” that maintain professionalism.

Reviewer Comment: “The authors should use whole-genome sequencing instead of targeted sequencing to identify off-target effects. Their current approach is insufficient for drawing conclusions about specificity.”

Your Response:

Response: We appreciate the reviewer's suggestion to employ whole-genome sequencing (WGS). However, we respectfully maintain that our targeted deep sequencing approach is appropriate and scientifically rigorous for the following reasons:

1. **Comprehensive coverage of predicted sites:** Our targeted panel includes all 547 sites predicted by three independent algorithms (GUIDE-seq, Cas-OFFinder, and CRISPOR) with up to 4 mismatches (Methods, page 10, lines 213-225). This captures >99.9% of sites likely to have any CRISPR activity based on current understanding of Cas9 specificity [citations].

2. **Superior depth for variant detection:** Our targeted approach achieves >10,000X coverage at each site, allowing detection of editing events at frequencies as low as 0.01%. WGS would provide only 30-50X coverage, potentially missing rare off-target events [Kim et al., 2020, Nature Biotech].

3. **Validation with orthogonal methods:** We validated our findings using GUIDE-seq (a genome-wide, unbiased method) in a subset of samples, confirming that our targeted panel captured all detected off-target sites (new Supplementary Figure S3).

4. **Standard in the field:** Recent publications in Cell, Nature, and Science using similar CRISPR systems have relied on targeted sequencing approaches [8 recent citations provided in revised manuscript].

To address the reviewer's underlying concern about comprehensiveness, we have:
- Added GUIDE-seq validation data (new Supplementary Figure S3)
- Expanded our discussion of methodological considerations and limitations (Discussion, page 21, lines 445-468)
- Clarified that our conclusions about specificity are limited to predicted off-target sites (Abstract and Discussion revisions)

We hope this explanation and the additional validation data demonstrate the rigor of our approach while acknowledging appropriate limitations.

Changes made: New Supplementary Figure S3 with GUIDE-seq validation; Discussion expanded (page 21, lines 445-468); Methods clarification (page 10, lines 213-225); Abstract revised (page 2, lines 34-36); 8 new references added (references 42-49).

Key Elements for Successful Disagreement:

• “We appreciate” or “We understand” opening (never “The reviewer is wrong”)
• Multiple evidence-based reasons (not just opinion)
• Citations supporting your position
• Acknowledgment of the reviewer’s valid underlying concern
• Compromise or additional data when possible
• Clear statement of any limitations
• Professional, evidence-based tone throughout

Red Flags to Avoid:

• ❌ “The reviewer doesn’t understand…”
• ❌ “This comment is incorrect…”
• ❌ “We obviously cannot…”
• ❌ “The reviewer should know that…”

Type 4: Misunderstandings (When Reviewers Miss Something)

When a reviewer comments on something you actually did address in your original manuscript, resist the urge to be sarcastic or dismissive. Instead, thank them for highlighting an area that needs better emphasis.

Reviewer Comment: “The authors did not discuss the potential cardiotoxic effects of their compound, which is a serious limitation.”

Your Response:

Response: We thank the reviewer for emphasizing the importance of cardiac safety, which we fully agree is critical for any therapeutic development. We did include preliminary cardiac assessment in our original submission (Methods section 2.5, page 9; Results section 3.4, page 17; Discussion page 22), but we recognize this may not have been sufficiently prominent given its importance.

We have now:
1. Added a dedicated Results subsection titled "Cardiac Safety Assessment" (Section 3.4, pages 17-18, lines 345-378)
2. Expanded our cardiac toxicity discussion in the Methods to detail the specific assays performed (troponin levels, ECG analysis, histopathology) (page 9, lines 198-215)
3. Added a new figure showing detailed cardiac function data over the 12-week treatment period (new Figure 5)
4. Discussed these findings more prominently in the Discussion, including comparison to known cardiotoxic compounds (page 23, lines 487-512)
5. Added this as a specific strength in our conclusions (page 25, lines 542-545)

We appreciate the reviewer drawing attention to this important aspect, as highlighting the favorable cardiac safety profile strengthens our manuscript significantly.

Changes made: New Section 3.4 "Cardiac Safety Assessment" (pages 17-18, lines 345-378); Methods expansion (page 9, lines 198-215); new Figure 5; Discussion expansion (page 23, lines 487-512); Conclusion revision (page 25, lines 542-545).

Key Elements:

• No indication that “we already said this” (even though you did)
• Framing as insufficient emphasis rather than reviewer error
• Substantial improvement to make the point impossible to miss
• Genuine appreciation for highlighting an important area
• Turning a negative into a positive (strength of your work)

Why This Approach Works: If the reviewer missed something, readers might too. By making it more prominent, you improve your manuscript while maintaining a collaborative relationship with the reviewer.

Type 5: Impossible or Unreasonable Requests

Sometimes reviewers request additional experiments that are beyond the scope of your study, prohibitively expensive, or would take years to complete. You can decline these requests professionally by:

1. Explaining why it’s not feasible
2. Discussing the current study’s scope and limitations
3. Suggesting it as valuable future work
4. Offering a reasonable compromise if possible

Reviewer Comment: “The authors should validate their findings in human clinical samples from at least 100 patients across multiple ethnic populations before drawing any conclusions about therapeutic potential.”

Your Response:

Response: We greatly appreciate the reviewer's suggestion to validate our findings in diverse human clinical samples. We fully agree that clinical validation is essential before any therapeutic application. However, this request is beyond the scope of the current preclinical study for several reasons:

1. **Study design and objectives:** Our manuscript focuses on establishing proof-of-concept in validated preclinical models (patient-derived xenografts and genetically engineered mouse models). This is the standard progression for early-stage therapeutic development [citations to similar Nature/Cell papers].

2. **Regulatory and practical constraints:** Access to 100+ patient samples across multiple ethnic groups would require multicenter IRB approvals and patient consent processes that typically take 18-24 months, which exceeds reasonable revision timelines. Furthermore, our institution's biobank has limited diversity in the specific cancer subtype we're studying.

3. **Resource requirements:** The reviewer's suggested validation would require approximately $250,000-$350,000 in additional funding and 24-36 months of work, essentially constituting an entirely separate clinical validation study.

To address the reviewer's valid underlying concern about clinical relevance and generalizability, we have:

1. **Expanded our limitations section** to explicitly state that clinical validation in diverse patient populations is needed (Discussion, page 24, lines 518-532)

2. **Added discussion** of how ethnic genetic variation might impact our findings, citing relevant pharmacogenomic literature (Discussion, page 24, lines 533-547)

3. **Proposed clinical validation as next steps** with specific study design considerations (Discussion, page 25, lines 548-565)

4. **Tempered our conclusions** to appropriately reflect the preclinical nature of our findings (Abstract page 2, lines 41-43; Conclusion page 26, lines 571-578)

5. **Added preliminary data** from three human tumor organoids (representing diverse genetic backgrounds) showing consistent responses (new Supplementary Figure S4). While this doesn't replace full clinical validation, it provides initial evidence of relevance across genetic contexts.

We believe our current work represents an important and complete preclinical study that appropriately establishes therapeutic potential while acknowledging the critical need for clinical validation in future studies. The scope and conclusions are consistent with similar preclinical studies published in high-impact journals [specific citations].

Changes made: Expanded limitations (page 24, lines 518-532); new Discussion subsection on clinical translation (pages 24-25, lines 533-565); revised Abstract (page 2, lines 41-43) and Conclusions (page 26, lines 571-578); new Supplementary Figure S4 with human organoid data; 6 new references on clinical translation and pharmacogenomics (references 67-72).

Key Elements for Declining Requests:

• Acknowledge the value of what they’re suggesting
• Provide clear, objective reasons it’s not feasible (time, cost, scope, access)
• Show you’ve thought seriously about the issue
• Offer what you CAN do (compromise data, better discussion of limitations)
• Frame declined work as “future studies”
• Adjust conclusions appropriately if needed
• Maintain respectful, professional tone

When to Push Back vs. Comply:

Push back when:

• Request requires 6+ months of additional work
• Request fundamentally changes the study’s scope
• Request requires resources unavailable to you
• Request reflects a misunderstanding of your study design
• Multiple other reviewers didn’t raise similar concerns

Consider complying when:

• Work can be completed in 2-4 weeks
• Request would genuinely strengthen your conclusions
• Multiple reviewers raise similar concerns
• The experiment is straightforward and low-cost
• Editor specifically emphasizes the importance

Tone and Language: Getting It Right

Your tone can make or break a rebuttal letter. The goal is professional, respectful, and confident—never defensive, dismissive, or overly apologetic.

The Right Professional Tone

Use these phrases consistently:

✅ “We appreciate this insightful suggestion…” ✅ “We thank the reviewer for identifying…” ✅ “We have addressed this concern by…” ✅ “We respectfully maintain our approach because…” ✅ “We understand the reviewer’s concern and have…” ✅ “The reviewer raises an important point…” ✅ “We have carefully considered this feedback…”

Avoid these phrases:

❌ “The reviewer is incorrect…” ❌ “This comment doesn’t make sense…” ❌ “We already explained this clearly…” ❌ “This is impossible to do…” ❌ “The reviewer obviously didn’t read…” ❌ “We strongly disagree…” ❌ “This criticism is unfair…”

Respectful Disagreement Framework

When you need to disagree, use this four-step structure:

1. Acknowledge: “We appreciate the reviewer’s suggestion to…” 2. State position: “However, we respectfully maintain our current approach…” 3. Provide evidence: “For the following reasons: [numbered list with citations]…” 4. Offer compromise: “To address the underlying concern, we have…”

Balancing Confidence and Humility

Too apologetic (undermines your work): “We apologize profusely for our terrible oversight. We realize our original manuscript was completely inadequate and we hope our modest improvements might possibly be acceptable…”

Too defensive (alienates reviewers): “The reviewer clearly misunderstood our approach. Our methods are standard in the field and need no justification. We will not be making changes to this section.”

Just right (professional and confident): “We appreciate the reviewer’s feedback on this section. We have clarified our methods to ensure the rationale is explicit (page X, lines Y-Z), and we’ve added citations to three recent high-impact studies using similar approaches [refs]. We believe this addresses the concern while maintaining the scientific rigor of our approach.”

Tone Examples for Different Situations

When agreeing and making changes: “We fully agree with this assessment and have substantially revised…”

When clarifying a misunderstanding: “We appreciate the opportunity to clarify this point. While we did include [X] in the original submission, we recognize it was not sufficiently clear…”

When respectfully disagreeing: “We understand the reviewer’s perspective. However, we believe our approach is appropriate for the following evidence-based reasons…”

When declining an impossible request: “We greatly value this suggestion. However, implementing this would require resources/time beyond the scope of the current study. Instead, we have…”

When multiple reviewers agree: “Both reviewers identified concerns about [X], and we are grateful for this feedback. We have thoroughly revised…”

When reviewers contradict each other: “We note that Reviewer 1 suggested [X] while Reviewer 2 suggested [Y]. We have attempted to balance these perspectives by…”

Common Scenarios and How to Handle Them

Beyond individual comment types, you’ll encounter specific situations that require strategic responses.

Scenario 1: Reviewers Disagree With Each Other

This happens frequently—one reviewer wants more detail, another wants brevity; one wants Method A, another prefers Method B. The key is acknowledging both perspectives and explaining your balanced approach.

Example Situation:

Reviewer 1: “The introduction is too brief. Add more background on the biological mechanisms.”

Reviewer 2: “The manuscript is too long. Consider moving some introductory material to supplementary files.”

Your Response:

Response: We recognize that Reviewer 1 requested additional background detail while Reviewer 2 suggested reducing length. We have attempted to address both concerns by:

1. **Adding key biological mechanism details to the Introduction** as Reviewer 1 suggested, specifically expanding discussion of the signaling pathway and its clinical relevance (Introduction, pages 3-4, lines 58-89). This adds approximately 200 words.

2. **Streamlining and removing redundant content** as Reviewer 2 suggested. Specifically:
   - Consolidated two paragraphs in the Introduction that repeated similar concepts (original pages 3-4 removed)
   - Moved detailed historical background to Supplementary Note S1 (formerly Introduction paragraphs 2-3)
   - Tightened the Discussion by removing speculative elements (removed ~150 words from Discussion)

3. **Reorganizing for better flow**, which improves both comprehensiveness (Reviewer 1's concern) and readability (Reviewer 2's concern)

The net result is an Introduction that is 50 words longer but more focused and informative, while the overall manuscript is 100 words shorter due to Discussion and Methods revisions. We believe this strikes an appropriate balance between the two reviewers' perspectives.

Changes made: Introduction expansion (pages 3-4, lines 58-89); new Supplementary Note S1; Discussion revised and shortened (page 22, lines 461-478); Methods tightened (page 10, lines 208-215).

Key Elements When Reviewers Conflict:

• Explicitly acknowledge both perspectives
• Don’t choose sides or favor one reviewer
• Show how you balanced competing concerns
• Quantify changes when possible (word counts, sections moved)
• Frame it as improvement, not compromise

Scenario 2: You Can’t Address All Comments

Sometimes you’ll have valid reasons for not implementing certain suggestions. Be strategic about which battles to fight and how to explain limitations.

Your Response:

Response to Comments 2.4-2.6: We have thoroughly addressed Comments 2.1 through 2.3, making substantial revisions to our experimental design and analysis. 

Regarding Comment 2.4 (conducting experiments in additional cell lines), we have partially addressed this by:
- Adding data from two additional cell lines (new Supplementary Figure S2)
- Expanding discussion of cell line-specific effects (Discussion, page 20, lines 412-428)

However, we respectfully note that Comment 2.5 (extending the observation period to 12 months) and Comment 2.6 (including large animal models) are beyond our current resources and timeline:

**For the extended observation period (2.5):**
- Our current study spans 6 months, which is standard for this type of analysis [citations]
- A 12-month study would delay publication by 6+ months
- We have added this as an explicit limitation and direction for future work (Discussion, page 23, lines 489-497)

**For large animal models (2.6):**
- Large animal studies would require $150,000-$200,000 in additional funding not currently available
- This typically constitutes a separate translational study following positive preclinical results
- We have discussed this as an important next step toward clinical translation (Discussion, page 25, lines 531-545)

We believe our current findings, based on rigorous cell culture and mouse models, represent a complete and significant preclinical study. The scope and conclusions are appropriately calibrated to the data we've generated and are consistent with similar studies in high-impact journals [specific citations].

Changes made: New Supplementary Figure S2 with additional cell lines; Discussion expanded to address limitations and future directions (pages 20, 23, 25); 4 new references on similar preclinical studies (refs 58-61).

Strategy for Partial Compliance:

• Show what you DID address (demonstrate effort)
• Explain objectively why you can’t do everything
• Mitigate with limitations discussion and future work
• Adjust conclusions if needed
• Maintain positive tone (not defensive)

Scenario 3: Multiple Comments About the Same Issue

When multiple reviewers identify the same weakness, this is both a red flag and an opportunity. Acknowledge it as a significant issue you’ve now fixed.

Example Situation:

Reviewer 1, Comment 3: “The statistical power analysis is missing.”

Reviewer 2, Comment 2: “How was sample size determined? Was the study adequately powered?”

Editor Comment: “Please address reviewer concerns about statistical power.”

Your Response:

Response to Reviewer 1 Comment 3, Reviewer 2 Comment 2, and Editor Comment:

All three reviewers identified the absence of statistical power analysis as a significant weakness, and we completely agree this was an important omission in our original submission. We thank the reviewers for this critical feedback.

We have now added comprehensive statistical power analysis throughout:

1. **A priori power calculations** for all primary experiments, showing that our sample sizes (n=8-12 per group) provide >80% power to detect effects of the observed magnitude at α=0.05 (Methods, new Section 2.8 "Statistical Power Analysis," page 11, lines 256-278)

2. **Post-hoc power analysis** confirming that our study achieved adequate power for all main conclusions (Supplementary Table S3)

3. **Sample size justification** based on preliminary data and published effect sizes from similar studies (Methods, page 11, lines 267-271)

4. **Discussion of limitations** for experiments where power was suboptimal (Discussion, page 24, lines 501-508)

We also consulted with a biostatistician (now acknowledged) who reviewed our power calculations and confirmed their appropriateness.

This addition substantially strengthens our manuscript by providing transparent justification for our experimental design and confidence in our conclusions.

Changes made: New Section 2.8 "Statistical Power Analysis" (page 11, lines 256-278); new Supplementary Table S3 with detailed power calculations; Discussion addition (page 24, lines 501-508); updated Acknowledgments to include statistical consultant.

Why This Approach Works:

• Immediately acknowledges agreement with multiple reviewers
• Shows you recognized the significance of the shared concern
• Provides thorough fix that goes beyond minimum required
• Thanks reviewers for improving the work
• Positions the revision as a major improvement

Scenario 4: Harsh or Unprofessional Reviewer Comments

Occasionally you’ll receive comments that feel personal, unnecessarily harsh, or unprofessional. Your response must rise above this and maintain perfect professionalism.

Example Harsh Comment: “The authors clearly don’t understand basic molecular biology. This experimental design is fundamentally flawed and the conclusions are not supported by the data.”

WRONG Response (Don’t Do This): “We strongly disagree with the reviewer’s characterization of our work. We are all PhD-level scientists with extensive expertise in molecular biology. The reviewer’s comment is inappropriate and appears to stem from a misunderstanding of our approach.”

RIGHT Response:

Response: We appreciate the reviewer's careful evaluation of our experimental design. We believe there may be a misunderstanding about our approach, which we aim to clarify here and in the revised manuscript.

[Then provide a clear, detailed explanation of your experimental design with:
- Step-by-step rationale
- Citations to similar approaches in high-impact journals  
- Acknowledgment of any limitations you're aware of
- Specific changes you've made to improve clarity]

We have substantially revised our Methods section to ensure our experimental design and rationale are crystal clear (Methods, pages 8-10, extensively revised). We've also added a new Supplementary Figure S1 showing validation experiments that support our approach.

We hope these clarifications address the reviewer's concerns about our experimental design and demonstrate the rigor of our methodology.

Changes made: Methods section 2.2-2.4 substantially revised (pages 8-10); new Supplementary Figure S1; expanded Results discussion of validation (page 15, lines 298-312).

Key Principles for Handling Harsh Comments:

• Never match their tone—stay professional
• Assume good faith (maybe they genuinely misunderstood)
• Focus on the scientific concern, ignore the tone
• Provide extensive clarification
• Improve the manuscript so no one else is confused
• Don’t mention the harsh tone to the editor in the response letter
• If truly inappropriate, contact the editor separately (not in the response)

Scenario 5: Comments That Reveal Reviewer Misunderstanding

Sometimes reviewers miss key information in your manuscript, leading to unfounded criticisms.

Reviewer Comment: “The authors did not control for batch effects in their RNA-seq analysis, which could substantially impact their conclusions.”

Your Response (They missed that you did this):

Response: We thank the reviewer for raising the important issue of batch effects in RNA-seq analysis. We did include batch effect correction in our original analysis pipeline (Methods, page 9, lines 187-194), using the ComBat method implemented in the SVA R package. However, we recognize this may not have been sufficiently emphasized given its importance.

To ensure this critical methodological detail is clear, we have:

1. **Added a dedicated subsection** on batch effect correction in the Methods (Section 2.6, page 9, lines 187-205)
2. **Created a new Supplementary Figure** (S2) showing principal component analysis before and after batch correction, demonstrating effective removal of batch effects
3. **Added explicit mention** in the Results when discussing RNA-seq findings (page 14, lines 287-289)
4. **Included batch information** in the sample metadata table (Supplementary Table S1, new column)

We appreciate the reviewer highlighting this important aspect of our analysis, as making it more prominent ensures readers understand the rigor of our approach.

Changes made: Methods Section 2.6 expanded (page 9, lines 187-205); new Supplementary Figure S2; Results addition (page 14, lines 287-289); Supplementary Table S1 updated with batch information.

Why This Works:

• No hint of “you didn’t read carefully”
• Frames as insufficient emphasis, not reviewer error
• Makes substantial improvements to prevent future confusion
• Thanks them for highlighting an important point
• Results in a better, clearer manuscript

Tracking Changes in Your Manuscript

One of the most critical but often overlooked aspects of rebuttal letters is clearly documenting where changes appear in your manuscript.

In Your Revised Manuscript

Most journals require you to submit two versions of your revised manuscript:

1. Marked/Tracked Changes Version:

• Use Microsoft Word’s Track Changes feature (turned ON)
• OR highlight all changes in yellow/color
• Clearly state in your response letter which method you used
• Some journals provide specific templates

2. Clean Version:

• Accept all changes (Track Changes turned OFF)
• No highlighting or markup
• This is what will be used for publication if accepted

In Your Response Letter

Every single response should include specific location information:

Essential Location Details:

• Section name: “Introduction,” “Methods,” “Results,” “Discussion”
• Page numbers: Current page numbers from the revised manuscript
• Line numbers: If your journal uses them (many do)
• Specific elements: Figure numbers, table numbers, supplementary materials

Good Examples:

Changes made: Introduction, pages 3-4, lines 68-92; Figure 2 caption revised; new Supplementary Figure S3.

Changes made: Methods Section 2.4 "Cell Culture Conditions" (page 8, lines 167-183); Table 1 updated with additional data; Supplementary Methods page S4.

Changes made: Throughout Discussion section - substantial reorganization (pages 19-23); added new subsection 4.3 "Clinical Implications" (page 22, lines 456-478); References 45-52 added.

Poor Examples (Don’t Do This):

Changes made: We revised the methods section.
[Problem: Which part? Where specifically?]

Changes made: See page 10.
[Problem: What changed? What should they look for?]

Changes made: We added more detail throughout.
[Problem: Not trackable, too vague]

Organizing Your Changes Document

Some authors create a separate “Summary of Changes” document in addition to the response letter. This can be helpful for extensive revisions:

SUMMARY OF CHANGES
Manuscript ID: JMB-2025-1234

MAJOR CHANGES:
1. New in vivo data added (Figure 4, pages 15-17, lines 312-367)
2. Methods section reorganized (pages 7-12, substantially revised)
3. Statistical analysis updated (throughout Results; new Supplementary Table S3)

MINOR CHANGES:
- Introduction streamlined (pages 2-4, lines 45-98)
- Discussion expanded to address limitations (page 22, lines 468-495)
- 12 new references added (references 38-49)
- All figure legends revised for clarity
- Typos corrected throughout

ALL CHANGES HIGHLIGHTED IN YELLOW IN THE MARKED MANUSCRIPT

Complete Response Letter Templates

Here are three templates you can adapt for different situations.

Template 1: Standard Response Letter (Mostly Agreement)

Dear Dr. [Editor Name],

Thank you for the opportunity to revise our manuscript titled "[Full Manuscript Title]" (Manuscript ID: [ID Number]). We sincerely appreciate the constructive and thoughtful feedback from both reviewers. Their comments have helped us improve the manuscript substantially, and we believe the revised version addresses all concerns raised.

Below we provide detailed point-by-point responses to each comment. All changes are highlighted in yellow in the marked manuscript version.

SUMMARY OF MAJOR REVISIONS:

1. [Most significant change with brief description]
2. [Second major change]
3. [Third major change]
4. [Additional major changes as needed]

──────────────────────────────────────────────────

REVIEWER 1

Comment 1.1: [Quote reviewer comment in italics]

Response: [Your detailed response explaining agreement and what you did]

Changes made: [Specific sections, pages, line numbers]

Comment 1.2: [Next comment]

Response: [Your response]

Changes made: [Locations]

[Continue for all Reviewer 1 comments]

──────────────────────────────────────────────────

REVIEWER 2

Comment 2.1: [Quote reviewer comment]

Response: [Your response]

Changes made: [Locations]

[Continue for all Reviewer 2 comments]

──────────────────────────────────────────────────

EDITOR COMMENTS (if any)

Comment E.1: [Editor's comment]

Response: [Your response]

Changes made: [Locations]

──────────────────────────────────────────────────

We believe these revisions have substantially strengthened our manuscript and fully address all reviewer concerns. We are grateful for the opportunity to improve our work through this rigorous peer review process.

Thank you for your consideration. Please don't hesitate to contact me if you need any clarification or additional information.

Sincerely,

[Corresponding Author Name]
[All Co-author Names Listed]

[Corresponding Author Full Title and Affiliation]
Email: [email]
Phone: [phone]
ORCID: [ORCID ID if applicable]

Template 2: Response With Significant Disagreements

Dear Dr. [Editor Name],

Thank you for the opportunity to revise our manuscript titled "[Title]" (Manuscript ID: [ID]). We appreciate the detailed feedback from the reviewers. While we have addressed most comments through revisions, we respectfully maintain our approach on several methodological points, as detailed below with supporting evidence.

SUMMARY OF MAJOR REVISIONS:

We have made substantial revisions including:
1. [Change made in response to reviewer feedback]
2. [Another change made]
3. [Clarifications added where we maintain our original approach]

All changes are highlighted in yellow in the marked manuscript.

──────────────────────────────────────────────────

REVIEWER 1

Comment 1.1: [Comment where you agree]

Response: We agree completely and have [your changes].

Changes made: [Locations]

Comment 1.2: "The authors should use Method X instead of Method Y."

Response: We appreciate the reviewer's suggestion to use [Method X]. However, we respectfully maintain our use of [Method Y] for the following reasons:

1. [Evidence-based reason with citation]
2. [Additional reason with citation]  
3. [Precedent from literature with citations]

To address the reviewer's underlying concern about [issue], we have:
- [Compromise or additional analysis you added]
- [Additional clarification in manuscript]

We have added a paragraph in the Methods section (page [X], lines [XX-YY]) explaining this methodological choice and its advantages for our specific research question, supported by citations to similar high-impact studies.

Changes made: [Locations of clarifications/additions]

[Continue with remaining comments]

──────────────────────────────────────────────────

REVIEWER 2

[Similar format]

──────────────────────────────────────────────────

We believe our revisions have addressed all substantive concerns while maintaining the scientific integrity and rigor of our work. Where we have respectfully disagreed with suggestions, we have provided evidence-based justifications and, where possible, offered alternative approaches to address the underlying concerns.

We are confident that these revisions have strengthened the manuscript and hope it now meets the standards for publication in [Journal Name].

Thank you for your consideration.

Sincerely,

[Authors]
[Contact Information]

Template 3: Response to Mixed Reviews (One Positive, One Critical)

Dear Dr. [Editor Name],

Thank you for the opportunity to revise our manuscript titled "[Title]" (Manuscript ID: [ID]). We appreciate the thoughtful feedback from both reviewers. We note that Reviewer 1 found our manuscript largely acceptable with minor revisions, while Reviewer 2 raised more substantial concerns. We have carefully addressed all points raised by both reviewers and believe the manuscript is significantly improved as a result.

SUMMARY OF MAJOR REVISIONS:

In response particularly to Reviewer 2's substantive concerns, we have:
1. [Major revision addressing key criticism]
2. [Another major revision]
3. [Additional significant change]

We have also addressed all of Reviewer 1's suggestions for improvement.

──────────────────────────────────────────────────

REVIEWER 1

We thank Reviewer 1 for their positive assessment and helpful suggestions for improvement.

Comment 1.1: [Minor comment]

Response: [Brief response and change made]

Changes made: [Locations]

[Continue with other Reviewer 1 comments - these should be relatively straightforward]

──────────────────────────────────────────────────

REVIEWER 2

We appreciate Reviewer 2's thorough and critical evaluation, which has helped us substantially improve our manuscript.

Comment 2.1: [Major concern]

Response: We thank the reviewer for this important feedback. We have addressed this concern by [extensive description of major revisions made].

Changes made: [Extensive locations]

Comment 2.2: [Another substantial concern]

Response: [Detailed response showing serious engagement with the criticism]

Changes made: [Locations]

[Continue addressing all substantial criticisms thoroughly]

──────────────────────────────────────────────────

We believe that our revisions, particularly in response to Reviewer 2's important feedback, have addressed all concerns and substantially strengthened the scientific rigor and clarity of our manuscript. The combination of Reviewer 1's positive assessment with Reviewer 2's critical insights has helped us produce a much stronger final version.

We hope that both reviewers will find our revisions satisfactory and that our manuscript now meets the high standards of [Journal Name].

Thank you for your consideration.

Sincerely,

[Authors]
[Contact Information]

Length Guidelines for Your Response Letter

A common question: “How long should my rebuttal letter be?”

Typical Lengths by Revision Type

Minor Revision:

• 2-4 pages typical
• Brief responses to straightforward comments
• Mostly agreement and clarifications

Major Revision:

• 5-10 pages typical
• More complex responses
• Some disagreements requiring evidence
• Multiple new analyses or experiments

Revise and Resubmit:

• 8-15 pages not uncommon
• Extensive revisions
• Significant new data
• Complex methodological discussions

The Real Answer: As Long as Necessary

Your response letter should be long enough to thoroughly address every comment. A response that’s “too long” because it’s comprehensive is infinitely better than one that’s “appropriately brief” but incomplete.

Guidelines for Individual Responses

Simple agreement: 2-3 sentences

Response: We agree and have corrected this error. Thank you for catching this.
Changes made: Page 12, line 234.

Clarification: 1 paragraph (4-6 sentences)

Response: [Acknowledge comment, explain the clarification you added, note where]
Changes made: [Locations]

Disagreement: 2-3 paragraphs (8-12 sentences)

Response: [Acknowledgment, your position, 3-4 evidence-based reasons with citations, compromise if possible]
Changes made: [Locations]

Complex methodological discussion: 3-5 paragraphs (up to 1 page)

Response: [Full justification with multiple evidence sources, detailed explanation, literature support]
Changes made: [Extensive locations]

Red Flags for Length

Too Brief:

• One-word responses: “Done.” or “Corrected.”
• Generic responses: “We addressed this.”
• No specific locations cited
• Signals: Lack of effort, dismissiveness

Too Long:

• 20+ page response letters (rare but happens)
• 2-3 page responses to minor comments
• Excessive repetition
• Might signal: Defensiveness, poor organization, inability to be concise

Just Right:

• Every comment thoroughly addressed
• Responses proportional to comment complexity
• Specific locations always provided
• Professional, clear, well-organized

Common Mistakes to Avoid

Even experienced researchers make these errors. Avoiding them immediately improves your chances of acceptance.

❌ Mistake 1: Ignoring or Skipping Comments

The Error: Not responding to every single comment, even minor ones.

Why It’s Harmful:

• Signals carelessness or inability to follow instructions
• Editors specifically check that all comments are addressed
• Even if a comment seems trivial, reviewers expect acknowledgment
• Can trigger automatic rejection

The Fix: Respond to EVERY comment, even typos:

Comment: "Page 5, line 103: 'teh' should be 'the'"
Response: Corrected. Thank you.
Changes made: Page 5, line 103.

❌ Mistake 2: Defensive or Argumentative Tone

The Error: Responding emotionally or defensively to criticism.

Examples of Defensive Language:

• “The reviewer clearly didn’t read our manuscript carefully…”
• “This criticism is unfounded and shows a lack of understanding…”
• “We strongly object to this characterization…”
• “The reviewer is wrong about…”

Why It’s Harmful:

• Alienates reviewers and editor
• Suggests you can’t handle professional criticism
• Makes reviewers less receptive to your arguments
• Can trigger rejection even if your science is sound

The Fix: Always start with appreciation, even when disagreeing:

WRONG: "The reviewer's suggestion to use Method X shows a fundamental misunderstanding of our system."

RIGHT: "We appreciate the reviewer's suggestion to use Method X. However, we believe Method Y is more appropriate for our specific system because [evidence-based reasons]. We have added clarification to the Methods section explaining this choice."

❌ Mistake 3: Responses Without Specific Changes

The Error: Saying you addressed something without indicating where in the manuscript.

Examples:

• “We have added more detail to the methods.”
• “We clarified this point.”
• “This has been revised.”

Why It’s Harmful:

• Reviewers can’t verify your changes
• Creates extra work for editor
• Suggests lack of organization or thoroughness
• Reduces trust in your responses

The Fix: ALWAYS include specific locations:

WRONG: "We have added more detail about the statistical analysis."

RIGHT: "We have added comprehensive detail about the statistical analysis in new Section 2.7 'Statistical Methods' (page 11, lines 245-268), including test types, significance thresholds, multiple comparison corrections, and power calculations. We have also added statistical details to all figure legends."

Changes made: New Methods Section 2.7 (page 11, lines 245-268); Figure legends 2-5 updated; new Supplementary Table S2 with complete statistical details.

❌ Mistake 4: Agreeing to Everything Without Thought

The Error: Automatically accepting every suggestion without critical evaluation.

Why It’s Harmful:

• Some suggestions might conflict with each other
• Some might not be scientifically appropriate for your study
• Looks weak or suggests poor scientific judgment
• Can compromise the integrity of your work
• Reviewers respect thoughtful disagreement more than blind compliance

The Fix: Critically evaluate each suggestion:

• Agree when reviewers are right
• Politely disagree with evidence when they’re not
• Offer compromises when appropriate
• Stand up for good science while staying respectful

❌ Mistake 5: Not Organizing Responses Clearly

The Error: Disorganized response letters that are hard to follow.

Examples:

• No clear separation between reviewers
• Comments not numbered or labeled
• Responses buried in long paragraphs
• No visual distinction between reviewer comments and your responses

Why It’s Harmful:

• Makes reviewer/editor work harder
• Increases chance they’ll miss something
• Suggests lack of attention to detail
• Professional appearance matters

The Fix: Use clear, consistent formatting:

• Separate reviewers visually (horizontal lines, headers)
• Number all comments (1.1, 1.2, 2.1, 2.2, etc.)
• Bold or italicize reviewer comments
• Use regular text for your responses
• Include white space for readability

❌ Mistake 6: Changing Your Mind Too Quickly on Scientific Issues

The Error: Immediately abandoning your approach when a reviewer questions it, even if you had good reasons.

Example: Reviewer: “The authors should use parametric tests instead of non-parametric tests.” Wrong response: “We agree and have changed all our statistical tests to parametric methods.” [Even though your data weren’t normally distributed and non-parametric was correct]

Why It’s Harmful:

• Compromises scientific integrity
• Might make your conclusions invalid
• Reviewers respect evidence-based decisions
• You know your data better than reviewers do

The Fix: Stand your ground when you’re scientifically justified:

Response: We appreciate the reviewer's suggestion to use parametric tests. However, we maintain our use of non-parametric tests because:

1. Shapiro-Wilk tests indicated our data significantly deviate from normality (p<0.001 for all groups; Supplementary Table S2)
2. Sample sizes are relatively small (n=8-10 per group), where non-parametric tests are more robust
3. Non-parametric tests make fewer assumptions about data distribution and are more conservative

We have added this justification to the Methods section (page 9, lines 198-205) with explicit mention of the normality testing results.

Changes made: Methods page 9, lines 198-205; new Supplementary Table S2 with normality test results.

❌ Mistake 7: Not Reading Instructions Carefully

The Error: Not following journal-specific requirements for response letters.

Common Oversights:

• Wrong file format (PDF vs. Word)
• Not highlighting changes in manuscript
• Missing required statements
• Wrong naming convention for files
• Not submitting all required documents

The Fix: Before submitting your revision:

1. Re-read the decision letter carefully
2. Check journal’s “Instructions for Authors Revisions” section
3. Follow any specific formatting requirements
4. Verify you’re submitting all required files:
   • Response letter
   • Revised manuscript (marked version)
   • Revised manuscript (clean version)
   • Supplementary materials
   • Any other requirements

What Happens After You Submit Your Rebuttal?

Understanding the process helps manage expectations and anxiety during the waiting period.

Typical Timeline

After submission:

• Week 1: Editorial office checks completeness, may request missing items
• Weeks 1-2: Editor reviews your response, decides whether to send to reviewers
• Weeks 2-6: Reviewers re-evaluate (if applicable)
• Weeks 4-8: Editorial decision

Variables affecting timeline:

• How busy the reviewers are
• Extent of revisions (major vs. minor)
• Whether you adequately addressed concerns
• Journal’s typical turnaround time
• Time of year (holidays slow things down)

Most journals aim for 4-8 weeks for revision decisions, though this varies widely. Learn more about journal decision timelines.

Who Reviews Your Revision?

Usually the same reviewers:

• Most journals send revisions back to original reviewers
• They can see your response letter
• They verify you addressed their concerns
• This is why tone matters so much

Sometimes new reviewers:

• If original reviewers are unavailable
• If you submitted very late (months after deadline)
• If editor wants fresh perspective
• For revise-and-resubmit decisions

Sometimes editor-only review:

• For minor revisions with straightforward changes
• When reviewers were positive but had small concerns
• When editor is satisfied with your responses

Possible Outcomes After Revision

According to analysis of types of journal decisions, here’s what typically happens:

Accept (30-50% of revisions):

• You addressed all concerns satisfactorily
• Reviewers are happy with changes
• Manuscript moves to production

Minor Revision – Another Round (30-40%):

• Most concerns addressed but a few remain
• Usually just 1-2 weeks to address
• Very high acceptance rate after this

Major Revision – Another Round (10-15%):

• Significant concerns remain
• Might need additional data
• Third round of review possible
• Consider carefully whether it’s worth continuing

Reject (5-15%):

• Failed to address fundamental concerns
• New issues emerged during revision
• Reviewers or editor not satisfied
• Learn what to do next

If You Receive Another Revision Request

Don’t panic. Multiple revision rounds are common, especially for high-impact journals.

Evaluate the decision carefully:

• Are the remaining concerns addressable?
• Is the timeline reasonable?
• Are reviewers being constructive or obstinate?
• Is this journal still your best fit?

If continuing:

• Address new concerns as thoroughly as the first round
• Reference your previous responses if relevant
• Maintain professional tone
• Consider whether reviewers are moving goalposts unfairly

If considering withdrawal:

• Sometimes appropriate if concerns are unreasonable
• Get co-author input
• Consider discussing with editor
• Have a backup journal in mind

Advanced Tips for Strong Rebuttal Letters

Beyond the basics, these strategies separate good responses from great ones.

Tip 1: Organize Complex Responses Logically

When addressing related comments together or reorganizing your response for clarity:

REVIEWER 1 Comments 1.2, 1.4, and REVIEWER 2 Comment 2.1 all relate to statistical power.

Response to Comments 1.2, 1.4, and 2.1:

We appreciate that multiple reviewers identified concerns about statistical power, indicating this was a significant weakness in our original submission. We have comprehensively addressed this by:

[Detailed response covering all three comments together]

This addresses:
- Reviewer 1 Comment 1.2: Sample size justification
- Reviewer 1 Comment 1.4: Power for subgroup analyses  
- Reviewer 2 Comment 2.1: A priori power calculations

Changes made: [Comprehensive list of locations]

Tip 2: Use Evidence Liberally

Support your responses with:

• Citations to literature: “This approach is standard in the field [refs 45-48]”
• Statistical evidence: “Power analysis indicates 85% power to detect effects of this magnitude”
• Methodological precedent: “Similar studies in Nature and Cell used this method [specific citations]”
• Preliminary data: “Pilot experiments showed [specific results]”

Tip 3: Highlight Improvements Generously

When changes strengthen your manuscript, say so explicitly:

“We thank the reviewer for this excellent suggestion. Adding these data has substantially strengthened our conclusions by…”

“This revision has improved the clarity of our manuscript considerably…”

“We appreciate this feedback, which led us to discover an additional finding that supports our main conclusion…”

Tip 4: Acknowledge Limitations Honestly

When you can’t do something or have legitimate limitations:

“We acknowledge this is a limitation of our study and have added explicit discussion of this constraint and its implications (Discussion, page 24, lines 512-528).”

“While we agree this would be valuable, it is beyond the scope of the current study. We have added this as an important direction for future research.”

Tip 5: Cross-Reference When Helpful

If you addressed one reviewer’s concern in a way that also addresses another’s:

“This revision also addresses Reviewer 2’s Comment 2.3 about [related issue].”

“As detailed in our response to Reviewer 1 Comment 1.4, we have added…”

Tip 6: Thank Strategically

Express genuine gratitude when reviewers:

• Identify real weaknesses you hadn’t noticed
• Suggest improvements that strengthen your work
• Catch errors or oversights
• Raise important points you should address

This builds goodwill and shows you value the peer review process.

Tip 7: Get Co-Author Buy-In

Before submitting your revision:

• Share response letter with all co-authors
• Ensure everyone agrees with how you addressed comments
• Get explicit approval for any disagreements with reviewers
• Verify all co-authors approve the revised manuscript

Disagreements among co-authors about how to respond can cause problems later.

Tip 8: Proofread Obsessively

Your response letter reflects your professionalism:

• Zero typos acceptable
• Perfect grammar required
• Consistent formatting throughout
• Accurate page/line numbers
• Verify all cross-references

A sloppy response letter undermines even excellent science.

Tip 9: Consider Timing

Don’t rush:

• Better to take a few extra days and be thorough
• Hasty responses often miss important points
• Quality matters more than speed (within reason)

Don’t delay excessively:

• Most journals give 4-8 weeks for major revisions, 2-4 weeks for minor
• Delays suggest lack of priority or difficulty addressing concerns
• If you need an extension, request it before the deadline
• Very late responses may trigger re-review by new reviewers

Tip 10: When in Doubt, Over-Communicate

If you’re unsure about a comment or what’s being requested:

Response: We want to ensure we fully address the reviewer's concern. We interpreted this comment as suggesting [your interpretation]. Based on this understanding, we have [your changes].

If we have misunderstood the reviewer's intent, we would be happy to make additional revisions upon clarification.

Changes made: [Locations based on your interpretation]

This shows good faith effort while inviting clarification if needed.

Frequently Asked Questions

How long should my rebuttal letter be?

As long as necessary to thoroughly address all comments—typically 3-8 pages for moderate revisions, up to 15 pages for extensive reviews. Each response should be detailed enough to demonstrate careful consideration. Brief responses like “Done” or “Corrected” without explanation signal insufficient effort.

Should I quote the entire reviewer comment?

Yes, quote enough of each comment so the editor and reviewers can immediately recall what was said, especially for longer reviews. For very brief comments (“Fix typo on page 5”), you can quote the whole thing. For longer comments, quote the key sentence or two and reference the comment number.

What if I fundamentally disagree with a reviewer?

Respectfully disagree with evidence. Use the framework: (1) acknowledge their perspective, (2) state your position, (3) provide multiple evidence-based reasons with citations, (4) offer compromise if possible. Never say reviewers are “wrong”—instead explain why your approach is scientifically appropriate. For more strategies, see our guide on alternatives to “we respectfully disagree.”

Can I add new data or analyses in my revision?

Yes, absolutely—if it addresses reviewer concerns or strengthens your manuscript. Be clear about what’s new and why you added it: “In response to Reviewer 2’s concern about [X], we performed additional experiments showing [Y] (new Figure 4).” Reviewers appreciate when you go beyond minimal compliance.

What if reviewers are factually wrong about something?

Politely correct with evidence, but assume it’s a clarity issue rather than reviewer error. Often when reviewers “miss” something, it means your manuscript wasn’t clear enough. Fix the clarity in your manuscript while diplomatically correcting the record in your response.

Should I respond to every single comment, even typos?

YES. Even for simple corrections write: “Corrected, page 5, line 103. Thank you.” Ignoring any comment, no matter how minor, signals carelessness and can trigger rejection. Editors specifically check that all comments are addressed.

What tone should I use throughout?

Professional, respectful, appreciative—even when disagreeing firmly. Phrases like “We appreciate,” “We thank the reviewer,” and “We have addressed this by” work well. Avoid defensive language like “The reviewer is wrong” or dismissive responses. Reviewers typically see your response letter, so maintaining positive relationships matters.

Can reviewers see my response letter?

Usually yes. Most journals send your response letter to reviewers along with your revised manuscript when they re-review. This is why maintaining a professional, respectful tone is critical throughout—even when you’re disagreeing with their suggestions.

What if my revision timeline is too short?

Contact the editorial office immediately to request an extension. Most journals will grant 2-4 additional weeks if you have a legitimate reason (ongoing experiments, co-author availability, teaching obligations). Never just submit late without requesting an extension—it looks unprofessional.

Should I mention that I’ve addressed concerns from multiple reviewers?

Yes, when multiple reviewers identify the same issue, explicitly acknowledge this: “Both Reviewer 1 and Reviewer 2 identified concerns about [X], and we agree this was a significant weakness. We have thoroughly addressed this by…” This shows you recognize important patterns in the feedback.

What if I need to collect new data but it will take months?

Be honest with the editor. If you believe the additional data is essential and doable, request a timeline extension explaining what you need to do and how long it will take. If the request is unreasonable or impossible, explain why in your response and offer alternatives (better limitations discussion, pilot data, different analysis). For guidance on whether extensive revisions are worthwhile, see our article on whether revise and resubmit is worth it.

Submitting Your Revision Package

When you’re ready to submit, ensure you have all required components properly formatted.

Complete Submission Checklist

Required Documents:

• [ ] Response/rebuttal letter (PDF or Word, per journal requirements)
• [ ] Revised manuscript with track changes or highlighting (Word/PDF)
• [ ] Clean revised manuscript with all changes accepted (Word/PDF)
• [ ] All figures (updated versions if changed)
• [ ] All tables (updated versions if changed)
• [ ] Supplementary materials (if any were added or revised)
• [ ] Cover letter to editor (if separate from response letter)
• [ ] Any additional required forms or statements

File Naming Best Practices:

ResponseLetter_MS12345_Smith.pdf
Manuscript_Revised_Tracked_MS12345_Smith.docx
Manuscript_Revised_Clean_MS12345_Smith.docx
Supplementary_Materials_Revised_MS12345_Smith.pdf
Figure1_Revised_MS12345_Smith.tiff

Before Clicking Submit:

• [ ] All page/line numbers in response letter match revised manuscript
• [ ] Track changes or highlighting is visible in marked version
• [ ] Clean version has all changes accepted (no markup visible)
• [ ] All figures/tables mentioned in response letter are included
• [ ] All co-authors have approved the revision
• [ ] Response addresses EVERY reviewer comment
• [ ] File formats match journal requirements
• [ ] No typos in response letter
• [ ] Contact information is current

Optional: Brief Cover Email to Editor

Some authors include a brief email to the editor when submitting revisions:

Subject: Revised Submission - Manuscript MS-JMB-2025-1234

Dear Dr. Martinez,

I am pleased to submit our revised manuscript "CRISPR-Mediated Targeting of Oncogenic KRAS Mutations" (MS-JMB-2025-1234) along with our detailed point-by-point response to reviewers.

We have carefully addressed all reviewer comments and believe the manuscript is substantially improved as a result. The most significant changes include [1-2 sentences on major revisions].

All changes are highlighted in the marked manuscript version, and specific page/line references are provided in the response letter for each revision.

Thank you for the opportunity to revise our work. Please let me know if you need any additional information.

Best regards,
Dr. James Chen

Note: Not all journals want or need this—check their instructions.

About The Author

This guide was written by Dr. James Richardson, a research engineer who has experienced manuscript rejection from both sides—as an author receiving disappointing decisions and as a reviewer whose critical feedback has contributed to rejection decisions. The strategies outlined here reflect what actually works for transforming revision requests into eventual publication success, based on both personal experience and analysis of hundreds of successful and unsuccessful rebuttal letters.

Dr. Richardson’s approach emphasizes respectful professionalism, evidence-based responses, and strategic communication—recognizing that peer review is fundamentally a collaborative process aimed at improving scientific communication, even when it doesn’t always feel that way in the moment.

Key Takeaways

Let’s distill everything into essential principles you must remember:

1. Address Every Single Comment

Never skip or ignore any reviewer comment, no matter how minor. Even typo corrections deserve acknowledgment: “Corrected, page 5, line 103. Thank you.”

2. Maintain Professional Tone Throughout

Always begin with appreciation, even when disagreeing. Use “We respectfully maintain” instead of “The reviewer is wrong.” Reviewers see your response letter.

3. Provide Specific Locations for All Changes

Every response must include exact page numbers, line numbers, section names, and figure/table references. “We revised the methods” is insufficient—”Methods Section 2.4, page 8, lines 167-183″ is correct.

4. Use Evidence When Disagreeing

Support disagreements with citations, data, and methodological precedent. “We believe” isn’t enough—”Three recent studies in Cell and Nature used this approach [citations]” is persuasive.

5. Acknowledge Valid Concerns Even When Disagreeing

When declining a suggestion, acknowledge the underlying concern and offer alternatives: “While we cannot collect data from 10 additional countries, we have expanded our limitations discussion and suggested this as valuable future work.”

6. Fix Clarity, Not Just Compliance

When reviewers miss or misunderstand something in your manuscript, don’t just explain in the response—improve the manuscript so future readers won’t be confused.

7. Show Genuine Appreciation for Good Feedback

Thank reviewers sincerely when they identify real weaknesses or suggest improvements that strengthen your work. This builds goodwill and demonstrates professionalism.

8. Organize for Maximum Clarity

Use clear formatting with numbered comments, visual separation between reviewers, and white space for readability. Make the reviewer/editor’s job easy.

9. Be Thorough, Not Brief

Better to provide too much detail than too little. A 10-page response that thoroughly addresses complex issues is better than a 3-page response that leaves questions unanswered.

10. Track Changes Meticulously

Submit both marked and clean manuscript versions. Ensure all page/line numbers in your response letter match the revised manuscript exactly.

Your Path Forward: Turning Revisions Into Acceptance

Receiving a revision decision isn’t rejection—it’s an opportunity. Studies show that manuscripts undergoing peer review revision have acceptance rates of 50-80%, dramatically higher than initial submission acceptance rates of 10-30% at most journals.

Your rebuttal letter is the bridge between the revision request and acceptance. By addressing every comment thoroughly, maintaining a professional tone even when disagreeing, and documenting your changes meticulously, you transform peer review from an obstacle into a collaborative process that improves your science.

Your Action Plan

Immediately after receiving reviews:

1. Read all comments completely before responding emotionally
2. Take a 24-48 hour break to process feedback objectively
3. Discuss with co-authors to ensure a unified response strategy

During revision: 4. Create an organized response document with all comments numbered 5. Draft responses addressing each point before revising manuscript 6. Make manuscript changes with track changes or highlighting enabled 7. Verify all page/line numbers match as you write responses

Before submission: 8. Have co-authors review both the response letter and the revised manuscript 9. Proofread response letter obsessively (zero typos acceptable) 10. Verify all required documents are included and properly formatted 11. Check that every single comment has been addressed

After submission: 12. Expect 4-8 weeks for editorial decision on revisions 13. Monitor submission system for status updates 14. Be prepared for possible additional minor revisions 15. Celebrate when accepted—you’ve earned it

Remember

Peer review is imperfect. Reviewers sometimes miss important points, misunderstand your approach, or request unreasonable additions. But the process generally improves manuscripts, and learning to navigate it effectively is an essential skill for successful academic publishing.

Your rebuttal letter demonstrates not just that you can do good science, but that you can communicate effectively, handle criticism professionally, and collaborate constructively with peers—all qualities that editors value highly.

Good luck with your revision, and may your well-crafted rebuttal letter lead to acceptance!

Have questions about responding to specific types of reviewer comments? Need help navigating a particularly challenging revision? Leave an comment below and explore our complete collection of guides on the peer review process, editorial decisions, and publication strategies.

Summary Table: Quick Reference Guide