The most probable cause is virus or malware.
Run an antivirus scan
Download and run malwarebytes.
http://www.malwarebytes.org/mbam.php

If negative
It may be shadow copies, system restore points taking up space

Download and check with this
WinDirStat - Free software downloads and software reviews - CNET Download.com

hi there. Most space is taken by system restore. it builds up over time. Even if you reformatted you Hard drive and reinstalled the OS restore takes up 15GB. So the more things you do like install or uninstall it will make a point. I reinstalled vista and as soon as it was done i disabled it and I got back 18GB of HDD space. IF YOU WANT to you can disable it. POST BACK if you want to do that.

hope this helps.

This is just a shot in the dark, but I had a similar problem with a Yahoo Messenger crash log. My entire 80GB hard drive was consumed by this one massive file! I don't know where this file is stored and can't verify because that was on my work computer.

However, you can see what files are causing this by seeing what files were last modified.
View Last Modified Files on Windows Vista - How-To Geek

An excerpt from there:

The simplest method that doesn’t require any additional software is to open up Vista’s Search panel (You can hit the F3 key while Windows Explorer is open).

Change the location to your C: drive or whichever drive you are trying to check, set the Date modified to today, and then check the box for “Include non-indexed, hidden, and system files”.

Press the Search button, and then make sure that the Date modified column is showing up in the list. If that column isn’t showing up, you’ll need to add it by right-clicking on the column area, choosing More and then checking the box for it.

You can then just sort by Date Modified descending to see all the recently changed files, which should give you some insight into what your computer is doing behind your back.

So, first thing in the morning, free up some space, wait a bit, and then do the above. Look at which files were modified, and you should see which files are taking up all the space. Hopefully that tells you something. For me, it was a crash log.