Search & Destroy cannot delete the HKYE_USERS\S-1-5-21. Any idea why

Probably because it's in use. Try booting up in Safe Mode (http://support.microsoft.com/kb/315222) then running Spybot (make sure it's updated).

Search & Destroy cannot delete the HKYE_USERS\S-1-5-21. Any idea why

I just wonder why you should want to delete this - or why S & D is trying to do so. Another question on this site asks "Have people had problems after deleting it.

There is the problem to be fixed so I was curios how to delete it. It seems that it won't bother to have HKYE_USERS\S-105021 in my computer.

Hi again,
The impression I got from other places on the net was that Spybot, though usually very good, sometimes comes up with a 'false positive' i.e. reports something that is not spyware, and that this is the case here. So, carry on regardless ! But I think you will find it is actually HKEY_USERS. That is what is usually found in the register.
K:)