I assume you're using the regular Apple mouse. If you're using some weird mouse, you may want to make sure that it's Mac certified.
Now if it's not the mouse, it's probably some hardware or driver that's causing the issue. Do you have a scanner hooked up to your Mac? Those can sometimes cause problems. Make sure you have the latest driver updates for any hardware installed on your system.
And if you have a lot of hardware, you can find out the culprit by process of elimination. First use your Mac for a while with only a keyboard and mouse hooked up, and then slowly and perihperals until it freezes (in this case, it might take awhile because it only happens occaisonally).
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