Perfusion of growth hormone inhibitory factor (somatostatin) into rat pancreas inhibited secretion of glucagon and insulin into medium containing 5.5 mM glucose. A 15-min infusionof arginine (20 mM) greatly increased glucagon and insulin secretion. When perfused simultaneously with arginine, somatostatin (55 nM) abolished the increase in glucagon secretion. The acute phase of insulin secretion in response to arginine was attenuated by somatostatin, and subsequentsecretion was decreased to control levels. Pretreatment for 5 min with somatostatin blocked evenacute-phase insulin secretion in response to arginine. Somatostatin did not affect basal or glucose-stimulated secretion of insulin from rat pancreatic islets isolated by the collagenase technique. Arginine-stimulated secretion of insulin was enhanced by somatostatin in isolated islets. These results demonstrate a direct effect of somatostatin on the pancreas to inhibit secretion of glucagon and insulin. The failure of somatostatin to inhibit insulin secretion in pancreatic islets may be due to alterations in the beta cells produced by the isolation procedure. It is also possible that the effect of somatostatin on insulin secretion may be mediated indirectly.(Endocrinology96: 370, 1975)