Well - Just in case anyone else comes across the same problem, I worked out what the deal was. Since I started this thread, the OS has gone from XP Pro to XP Home to Win 98 and back to XP Pro.
This problem had nothing to do with Safedisc & Macrovision, it was all in the Secondary IDE Channel.
Device Manager -> IDE Controllers -> Secondary IDE Channel -> Advanced -> change to PIO instead of either BIOS default / DMA 2.
I doubt this is something that I will ever forget!
