Using rat isolated pancreatic islets, we investigated the effects of various alpha-adrenoceptor blocking agents on adrenaline-induced inhibition of glucose-stimulated insulin release. Yohimbine was about 100 times more potent than prazosin in antagonizing the inhibitory effect of adrenaline. At concentrations of 10 micro M, phentolamine was about as effective as an antagonist as yohimbine, whereas dihydroergotamine, WB-4101 and phenoxybenzamine were less effective and prazosin produced very little antagonism. These results strongly suggest that post-synaptic alpha 2-adrenoceptors modulate insulin release from pancreatic islets.