What version of Exchange is it, and on what OS?  What's the size of the IS?  
Does it happen during, say, a backup or an online defrag?

The first thing I'd try are the non-destructive eseutil options - the /D and /G 
defrag and integrity check options.

Check with the users, see if anyone's trying to send out some kind of regular 
bulletin to all users at that time.  Check your MTA queues and see if they're 
backlogged before it happens.
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