This study was undertaken to determine the influence of alpha-adrenergic blockade upon the somatostatin-mediated inhibition of insulin secretion. Somatostatin inhibited both the basal and glucose-stimulated pancreaticoduodenal vein insulin output of dogs. This effect was not observed during a simultaneous infusion of phentolamine, an alpha-adrenergic blocker. It is proposed that alpha-adrenergic mechanisms play a role in the inhibition of insulin secretion by somatostatin.