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Duff-Man says...maybe try a re-index. Since Mail isn't opening you need to do it the manual way. In your ~/Library/Mail/V2/MailData folder find the 3 "envelope index" files and either copy them to another spot (in case you need them back!) then delete the originals, or just move them to another spot for safekeeping until you're sure you don't need them back. Then try launching Mail again, it may take a little bit to rebuild the index.

If that doesn't work, then maybe try the same thing with the Mail plist file (in the preferences folder of course)....oh yeah!
 
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