Here's the notable specs of the machine. While troubleshooting I've removed everything else and had only the Megamix installed and then worked back into adding the hardware so I am pretty sure it is a software conflict.
Hardware:
A4000D in a Power tower enclosure
Mediator PCI 4000D 3V MK-III
SoundBlaster 128
Voodoo 3
Spider II USB
Indivision MK2
ZorRAM 128 MB
Software:
Amiga OS 3.9
Boing Bag 1,2 3 & 4 installed
Let me know if there is anything else relevant worth sharing. I'd be happy for tips on how to track down such a conflict in general.