It could literally be anything. I have an old WD 20GB drive from like 6 years ago. One day, as I was transfering it over to an older machine, popped it in, then heard this insanely loud (And I mean LOUD) whine. Sounded like a regular drive, except amplified maybe by 25 times as loud. I thought the platters were spinning so fast that they would shatter inside the drive or something. I was scared to hell, as at the time I couldnt afford a replacement. I ran every diagnostic known to man... Well, maybe not every one, but I ran several.
There were no problems with read/write activity whatsoever. I did a clean format, used a different power connector, and replaced the IDE ribbon. The horrendous noise was still there. So I decided to have fun with it and see how long I can torture it before it went. I installed XP, did a full 6-part chkdsk (the kind that usually take a day to finish), then a full defrag. After it was all over, nothing had changed. It read well, and it wrote well. Response times were perfectly fine.
Anyway, it's been almost a year since I have had that drive with an incredible irritating screeching whine, and it hasnt failed me once within the time frame. However, my current 60GB drive just failed on me without any warning. Just goes to show you, mysterious noises can commonly be nothing more than a scare.