iTunes Links
What system are you running?
As you may know, iTunes does not physically move files around within the program. Rather, it creates links from the Playlist to the file and vice versa... sort of like the way a web page links to an image, but doesn't embed the image in the html file.
Anyway, if you created all these playlists and then moved the MP3's to another HD... that's the problem! Most likely, iTunes was looking for "song.mp3" on "YourMainHD

ocuments:iTunes:Music:Song:song.mp3". Then you moved it to "NewFireWireHD:Anywhere:song.mp3" and iTunes didn't know where to look. I don't think there's a way to "relink" files in iTunes, but I'm not sure. It could likely be done in AppleScript.
Regardless, know the location of these important files and make back-up copies of them "iTunes Music Library", "iTunes Music Library (2)" (if any), "iTunes EQ Presets", and "iTunes Preferences". The latter two are probably in your System Folder

references:iTunes. The first two should be in your Documents folder (as this is iTunes default). These files provide all the information to iTunes to "remember" your EQ settings and playlists.
That's all the help I can provide for now, until I know more about what's happening. (ie: "So, then I turned on the computer the next day and got a crashing car sound...")
Here's what I always tell my mother:
1) Restart the computer
2) Re-install the software (in which case I have to do it)
3) The computer **usually** only does things that you tell it to do
Who knows? Could be a screwy "no-ones-ever-heard-of- iTunes-doing-this-before" kind of thing. In which case, I can offer no more help.