The present study was undertaken to characterize the effects of BPDZ 62, an original pyridothiadiazine derivative structurally related to both diazoxide and pinacidil, on ionic and secretory events in the rat pancreatic islet cells. BPDZ 62 increased the rate of 86Rb outflow from islets perfused in the presence or absence of extracellular glucose. These effects persisted in the absence of extracellular Ca++ but were abolished by glibenclamide. Such data support the view that BPDZ 2 activates ATP-sensitive K+ (K(ATP)) channels. This proposal was substantiated by the finding that the drug enhanced the flow of current through K(ATP) channels in excised inside-out membrane patches. BPDZ 62 markedly decreased 45Ca uptake, 45Ca outflow and insulin output from islets incubated in the presence of 16.7 mM glucose. By contrast, the drug did not affect the increase in 45Ca outflow and 45Ca uptake mediated by K+ depolarization. In single B cells, BPDZ 62 inhibited the glucose but not the KCl-induced rise in [Ca++]i. It is concluded that the inhibitory effect of BPDZ 62 on the insulin-releasing process results from the activation of K(ATP) channels leading to a decrease in Ca++ influx and [Ca++]i. Last, BPDZ 62 was shown to be five times more potent than diazoxide at inhibiting the insulin-releasing process. This suggests that BPDZ 62 could be a valuable pharmacological tool for further characterization of B-cell K(ATP) channels.