I've noticed Sophos Anti-Virus for Mac OS X locks up iTunes for lengthy periods of time after downloading a really large app.
The navigation app I use on my iPhone contains all the maps for the entire continent, so its updates are greater than 1GB in size. On downloading a fresh update of this app, iTunes stopped responding for many minutes. The behavior was repeatable, and investigation showed the InterCheck process--a piece of Sophos' scanning technology--was my machine's top CPU-cycle consumer during this period, eating more than 30% of my CPU.
Eventually the process completes, allowing iTunes to resume responding and dropping InterCheck down to its normal minuscule CPU usage.
Whitelisting ~/Music/iTunes/iTunes Music/ in Sophos' Preference|On-Access Scanning|Exclusions should solve the issue. Of course, you're trusting Apple to not distribute malware-laden apps and other content-- but one would hope that's a fair bet.
Details:
OS X 10.6.6
Sophos Anti-Virus for Mac Version 7.2.4C
Threat detection engine: 3.16.1
Threat data: 4.62
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