The present studies have demonstrated that the growth hormone release-inhibiting factor of the hypothalamus, somatostatin, exerts a prominent inhibiting action on glucose induced insulin release in man. This inhibition of insulin release could not be reversed by infusion of the α-adrenergic blocking agent, phentolamine. Our findings therefore suggest that the inhibiting effect of somatostatin on glucose induced insulin release is not mediated by the α-adrenergic receptors.