The rate of insulin, glucagon, and somatostatin secretion was measured from isolated rat islets maintained in a perifusion system. The effect of norepinephrine (NE) was simultaneously determined on the release rate of all three hormones. Norepinephrine was employed at an acute dose of 10 μM and in graded doses from 1 nM to 10 μM in the presence of high (22 mM) and low (1.4 mM) glucose concentrations. Under both high and low glucose conditions, insulin secretion was maximally inhibited at 10 μM NE concentration and was significantly depressed at 100 nM NE concentration. Under both high and low glucose conditions, glucagon release was maximally stimulated at 10 μM NE concentration and was significantly elevated at 10 nM NE concentration. Under high and low glucose conditions, somatostatin release was inhibited by 10 μM NE concentration and was significantly depressed at 100 nM NE concentration. During the initial maximal stimulation of glucagon, NE inhibition of somatostatin and insulin was prevented, possibly by the high level of glucagon released. A paracrine effect of glucagon on beta and delta cells is proposed.