Endogenous opiates have been suggested to have effects on insulin secretion. In order to investigate the in vivo importance of endogenous opiate receptor agonists on basal and stimulated insulin secretion, the effect on plasma insulin of opiate receptor blockade by naloxone was studied in the mouse. It was found that the plasma insulin levels in naloxone-injected mice were moderately lower than in the control animals after 5 min. Ten minutes later, however, naloxone-injected animals had slightly higher plasma insulin levels than did the controls. Naloxone moderately potentiated the insulin secretory responses to glucose and the beta 2-adrenoceptor agonist terbutaline. On the contrary, naloxone had no apparent effect on the insulin secretory response to the cholinergic agonist carbachol or the synthetic C-terminal octapeptide of cholecystokinin, CCK-8. In conclusion, endogenous opioid substances might moderate the regulation of basal insulin levels in the mouse. Further, they seem to have the capability to modulate the insulin release stimulated by glucose or beta-adrenoceptor agonists.