I had a similar situation recently on Win XP Pro.
Problem: I needed to put an interface cable on COM 2 but after physically connecting it to the COM 2 I found that the computer wouldn't talk to it.
My solution (eventually) was to firstly confirm that COM 2 was being used by something else. I downloaded the free programme ComChk32 from
here. After extracting/unzipping and running the programme I got a red square against COM 2 which showed that the port was talking to something else. (I used this programme to try to prove that it was the computer that was blocking me from COM 2 and not my interface cable that was faulty).
Next I realised that although I was now on Broadband via a USB modem the computer had originally been used on dial-up using a modem on COM 2. I then deleted all hardware references to the long disconnected modem and re-ran ComChk32 but was still locked out from COM 2. I then went into Control Panel and Network Connections to find my Dial Up connections and deleted my dial up Freeserve connection and re-ran ComChk32 and got a green light and tried my peripheral on COM 2 and found that it had now come to life. (I might have rebooted the computer after the deletions and before running ComChk32, I can't remember.)
I am not an expert by any means so someone else may well have a better idea but this solved my problem.
Best of luck as I fully understand your frustration.