External hard drive seems to block applications randomly Since updating to OSX Lion on my late 2009 iMac, I have noticed some strange behaviour while using my computer.  Every hour or so (I'm not actually sure about this pattern), the application that I am using will suddenly freeze. I will then hear my external hard drive spin up, and eventually, the application will begin to work again.

As an example, simply right-clicking on something in Chrome or half-way through watching a video in Plex will cause the entire application to freeze until the disk is spinning again. I can't think how these applications could possibly rely on this external disk, as all I use it for is my Time Machine back-up.

I have disabled the "put hard disks to sleep when possible" option, but this doesn't appear to have fixed anything. One possible explanation could be that this external disk is being used as part of virtual memory; it would explain the OS's reliance on the disk, but I can't imagine why it would do that when I have plenty of disk space remaining on my system drive.

This isn't entirely fatal, it's more annoying than anything else, but I am concerned that this could indicate that something is wrong with my operating system or hardware. I would be grateful for any ideas.
It might be the Spotlight indexing. Do you see mdworker active in Activity Monitor when this happens? If you have not done this yet, you might try excluding the drive in the Spotlight Privacy settings in System Preferences and see if that helps.