Well it would be helpful to know what type of system you are running iTunes on.

Aside from that your real problem most likely has little to do with your library and is an issue with your hard drive (see my post in this thread for more details). iTunes is constantly accessing your hard drives as is typical of (proper) database design.

iTunes is always initially sluggish when I attempt to do something after waking the computer or if the drive that my content is stored on has spun down; I can hear the drive accelerating whenever I get the spinning beach ball. Once the drive has spun up it is most operations work as expected. The same thing occurs when I create or modify records in my Music Collector database. So what you are likely facing is a disk latency issue.

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“Cannot run out of time. There is infinite time. You are finite. Zathras is finite. This is wrong tool.” 2.3GHz Power Mac G5/8GB/2x1TB HDD/OS X 10.4.11/30-inch ACD, 60GB iPod (Color)