To run defrag, you need to turn off everything else that is running. Be sure to get all TSR's. Sometimes it's difficult to stop everything, so here's a nifty little tool that will do it for you. My husband uses this all the time. He really likes it. There's a freeware version here. That's what he uses.
[url]http://www.powerdefrag.com/[/url]
Also, run defrag twice in a row. The first time will defrag your files and folders...the second will defrag your O/S.
The next thing you need to worry about is what is eating up your hard drive. Double and triple check for viruses. It sure sounds like you have one. If you're absolutely sure you don't have one, then you need to do a surface scan on your hard disk. You might have bad sectors.
That's the best I can tell you with the information that you gave. Good luck!