I can't seem to reproduce this consistently, but I figure I should pass this along to see if anyone else has any ideas.
Using VSYNC with multiple monitors has a rough 50% chance of causing MAME to run normally until the emulation starts (read: pre-start warnings about not supporting cocktail rotation work fine) but once the game actually starts up, MAME stops taking input at all and has to be end-tasked.
It MIGHT be multithreaded-related, as turning that on seems to have made it worse, but I'm not 100% sure. I don't have enough to go on to get this to MAMETesters, so I figure my best bet is to get this one over here to see if anyone else can reproduce it.
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Try checking the MAME manual at http://docs.mamedev.org
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