Exchange 5.5 admin

There is a size limit of 16 Gb if your run Exchange srvr 5.5 std. edition (Enterprise edition has no limit). Check the size of dir.edb.

Check that there is disk space on all drives of the server.

Check how much memory your server uses, there seems to be a leak in the store.exe or store.dll which demands a reboot every now and then (weekly).

Check eventlog for errors and search for them at Google or similar search engines.

Good luck!