Deleting Prefs and DDB's is always worth a shot with random problems like these. Failing that, it maybe some kind of RF interference. Do the cables to your monitors pass near anything that might cause interference (e.g VGA monitors).
Also, there's a bit on Answerbase about Mbox interference issues (reproduced below),
Mbox or Mbox 2 experiences whine or high pitched noise while in use.
The problem is related to either the computer itself, or to ground loops induced by plugging gear into multiple outlets or just plain bad grounding. The Mbox is generally not the culprit.
The following steps can help resolve the issue:
1) Plug all gear into the same outlet and/or make sure your outlets have a good ground.
2) Use TRS (balanced) cables from the outputs of the Mbox.
3) Get a Monster 'Ultimate Performance' USB Cable
If you are on a G5 and the above recommendations don't help, you can install the Apple Developer Tool called CHUD which helps remove noise cause by the processor to be eliminated.
More information on installing CHUD: http://www.digidesign.com/index.cfm?...1&itemid=20534
Further troubleshooting and help with 60 cycle hum issues
http://www.myspace.com/philogg