If the BizTalk message box database, by default BizTalkMsgDb, or the log file for that matter, gets too large, performance of the database subsystem will be affected considerably.

If your message box has grown too large and Biztalk becomes unresponsive, you might want to clean up the database manually, to do so check this link.

As a side note, I tend to get warning signals when I need to clear out the message box database when my webservices running under the Biztalk isolated host become increasingly slow to send messages to the database.