The plasma insulin response to iv administered glucagon was studied in five healthy subjects both in the basal state and during insulin induced hypoglycemia. Insulin response to glucagon was blunted when the blood glucose level was decreased. This inhibition was not entirely mediated by catecholamines liberated during hypoglycemia, since the alpha adrenergic blocking agent phentolamine could not restore the effect of glucagon. Phentolamine itself, in the absence of hypoglycemia, had no significant effect on glucagon induced insulin release.It is concluded that, in man, the insulin releasing action of glucagon is dependent on the presence of a normal blood glucose concentration.