Conditional acceptance then rejection – worthy of appeal? We submited a manuscript to an Elsevier journal eight months ago – we basically got a clear straight-forward rejection: 


  Although the reviewers commented favourably on your manuscript, there were significant criticisms that preclude publications. These comments indicated that your manuscript has some serious weakness. We would be willing to reconsider the manuscript after it has undergone a major revision that takes into account the criticisms of the reviewers, with no assurance of acceptance


We spent about seven months, performing more experiments and answering all concerns raised and we resubmitted. We thought we received a conditional acceptance. Two reviewers replied that we addressed all their concerns, third reviewer however commented that the work cannot be possible (simply based on his/her belief) and went on to ask a few things that is not really relevant and suggested that we discuss a big bunch of stuff unrelated to our study in the discussion (i.e., add a lot of speculations). 


  The reviewers commented favorably on your manuscript, but had some worthwhile suggestions. I am pleased to accept your manuscript, based on your revising it according to the recommendations of the reviewers" 


So we followed the third reviewer’s suggestions and amended accordingly. We did a couple more experiments, all supporting that our initital conclusions were correct. Then 2.5 weeks later, we got a rejection:


  I regret to relate that your manuscript cannot be accepted for publications. In addition to the comments of the outside reviewer’s, the editors have considered whether merely editorial or technical corrections would result in a priority score sufficient for acceptance, by comparison to other manuscripts we currently receive.


No new reviewer comments were included. Prior to sending us the decision, the editor did contact us about declaring whether a western blot was cropped.

We were expecting that the journal would accept it, as it stated: “I am pleased to accept your MS”. I felt like that we received a conditional acceptance but now a rejection. So did I get a rejection because our western blot is cropped? If they really don’t like that, we can always re-run the gel and present non-cropped images (these images are not presented in the manuscript, but on the response to reviewers only). Is this the reason why our manuscript was rejected?

It is worthwhile to appeal? Or would I be wasting time? If we didn’t receive a high priority score, why did they indicated conditional acceptance in the second decision letter? 

I would really like to hear some honest opinions, cause my own ones are likely to be biased influenced by my frustration and disappointment.
I believe you have misunderstood what the first "acceptance" meant (which could have been worded better to prevent this).

A journal generally has many editors and an editorial board. 

The typical journal review structure has your paper go to a single editor, who decides if the paper passes first muster and assigns reviewers if so.  Once the review process is complete, that editor then decides if the paper is to be rejected, revised, or advanced to the full editorial board. Your "conditional acceptance" seems to be the first editor advancing the paper to the full editorial board.  The board then made the final decision to reject the paper.  Note that some journals (in some fields) can have a high rejection rate from the editorial board. So while that initial "acceptance" can feel like a victory you're not actually out of the woods yet.

I expect your chances for a successful appeal to be small.  The decision seems only slightly based on your paper and mostly on the technical details of how the journal selects publications.  They're unlikely to bend those to your benefit.