Nicotinamide (10 mmol/kg) and 3-aminobenzamide (1.25 mmol/kg), poly(ADP-ribose) synthetase inhibitors, were injected intravenously to rats either 30 min before the intravenous administration of 12 mg/kg alloxan or 50 mg/kg streptozotocin ("pretreatment") or 5 min after the administration ("posttreatment"). Fifteen minutes after the injection of the diabetogenic agents, pancreatic islets were isolated from the rats and proinsulin synthesis was determined. Proinsulin synthesis was decreased in islets from rats treated with alloxan or streptozotocin. Pretreatment with poly(ADP-ribose) synthetase inhibitors was found to protect against alloxan- or streptozotocin-induced decrease in proinsulin synthesis. By posttreatment with poly(ADP-ribose) synthetase inhibitors, streptozotocin-induced decrease in proinsulin synthesis was also significantly reversed, whereas the decrease induced by alloxan was not.