This study aimed at investigating the effect of exogenous prostaglandin E1 (PGE1) administration on both basal and glucose-stimulated insulin secretion in normal man. For this purpose, six normal subjects were submitted to an infusion of PGE1 (0.2 microgram/kg/min) over a period of 75 min. Plasma glucose exhibited a progressive increase whereas insulin did not show any significant change. In order to exclude the participation of endogenously released catecholamines in these responses to PGE1, six additional subjects received PGE1 60 min after the start of the infusion of the alpha-adrenergic blocking agent phentolamine. Hyperglycemia developed during the combined infusion of phentolamine plus PGE1, but plasma insulin remained essentially unchanged. In other six normal volunteers, PGE1 (0.5 microgram/kg/min) significantly reduced both insulin response to intravenous glucose and glucose tolerance. These results seen to indicate that an intraislet synthesis of prostaglandins is involved in the beta-cell regulation of insulin release.