The effects of islet-activating protein (IAP) on the contractile responses of vas deferens to exogenous norepinephrine (NE) and electric stimulation (ES) were investigated. IAP treatment had no effect on the contractile response to NE. Pretreatment of the vas deferens with IAP (2.0 micrograms/ml) for 2 h however significantly attenuated the inhibitory effect of clonidine on ES-induced contractile responses, suggesting that feedback inhibition of presynaptic alpha 2-adrenoceptors is mediated by the Ni subunit of presynaptic adenylate cyclase.