If you have the indexing on, then it will indeed be busy until it gets done. Combine this with your antivirus and it's going to be the rare machine that is not reading the HDD.
With that out of the way, there are hardware reasons but your post didn't list the make, model, age, HDD type and such.
My Win 7 (64 bit) computer with a Intel i5 760 CPU, 4Gb of ram and AT Radeon HD 7500 Graphics card has developed a problem with about 25% constant CPU activity and constant disc activity. Task Manager shows that this is due to the "NT Kernel and System" process, and it can't be stopped. The surprising thing is that I get exactly the same problem in Safe Mode with no connection to the Network, so what the heck is going on?? Has anyone come across the same problem and is there any solution short of a complete re-installation?