omega-Conotoxin GVIA and omega-conotoxin MVIIC caused similar concentration-dependent reductions of the electrically induced twitch responses of guinea-pig ileum. The inhibitory effects of omega-conotoxin GVIA were long-lasting whereas those to omega-conotoxin MVIIC were readily reversed. Preincubation with omega-conotoxin MVIIC prevented the irreversible inhibition of omega-conotoxin GVIA suggesting a common site of interaction. However, unlike omega-conotoxin GVIA which caused inhibition, omega-conotoxin MVIIC did not affect the electrically induced twitch responses of the rat vas deferens nor did it prevent the irreversible inhibition with omega-conotoxin GVIA. This study indicates the possible existence of different subtypes of the N-type voltage-dependent calcium channel.