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We only scan on writes and exclude:
C:\Documents and Settings\All Users\Application Data\McAfee\Common Framework
C:\Windows\System32\CCM (SMS client)
Just be aware scanning only on writes is only safe if you NEVER connect an external device like a thumb or hard drive. You want to catch anything before it's running and trying to write to your local drive.
Is there a way to set separate setting for internal and external drives? The only options I'm aware of are for drives and network.