The actions of efaroxan, a highly selective and potent alpha 2-adrenoceptor antagonist, on insulin secretion, cAMP levels, 86Rb+ efflux and ATP-regulated potassium (K+ATP) channels have been studied using isolated pancreatic islets of Langerhans and RINm5F cells. In the absence of an adrenoceptor agonist, efaroxan (1-100 microM) potentiated glucose-induced secretion over the range 4-10 mM glucose, but was without effect upon the maximal rate of secretion induced by 20 mM glucose. Efaroxan did not affect cAMP levels. Suppression of insulin release by the potassium channel opener diazoxide, was partially alleviated by efaroxan and was associated with an inhibition of the diazoxide-induced increase in the rate of 86Rb+ efflux. Using isolated patches of membrane we found efaroxan to be an effective blocker of K+ATP channels, with a KI value of 12 microM and a Hill coefficient of approximately 1. These data indicate that efaroxan promotes insulin secretion, in the absence of exogenous agonists, by a mechanism that involves inhibition of ATP-regulated K+ channels.