Hi there, I have the same problem. Quadcore PC running Vista with corded USB optical mouse. After a while, it would stop responding to left mouse clicks. Since then I have installed a new hardrive and a clean install of Windows 7 Pro. I still get the same problem! I've tried another, corded mouse (non-optical), in different ports. So, it's not the operating system, it's not the mouse and it's not a particular USB port. All points to the whole USB bus perhaps? However, here's the thing - if I do Ctrl-Alt-Del, roll the cursor down to start task manager, the left mouse key springs back into life...!