I recently lost the clickability of my Desktop icons -- a double-click on an icon on my Desktop did nothing. To add to the confusion, double-clicks in windows would work fine, but a double-click on an email in Apple's Mail didn't work. After spending hours trying to debug the problem, it suddenly occurred to me that I had (hours earlier) set my mouse double-click speed to fastest (in the Keyboard & Mouse System Preferences panel). Since double-clicks in windows worked fine, I hadn't notice this bug until hours later. For some unexplained reason, the Desktop (Finder) and Mail couldn't pick up double-clicks on the "fastest" mouse setting. Pulling the double-click speed back one notch fixed the problem. [robg adds: I can confirm this problem exists on my MacBook Pro as well.]

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