The effects of adrenergic blockers on the glucagon response to insulin hypoglycemia were investigated in diabetic (10-15 days poststreptozocin [STZ] injection) and age-matched control rats. alpha-(Phentolamine nonspecific but predominantly alpha 1), alpha 2-(yohimbine), or beta-(propranolol) adrenergic blockers alone or in combination did not affect plasma glucose levels or plasma glucagon concentrations, in the basal state, in either control or diabetic rats. None of these adrenergic blockers, alone or in combination, inhibited the glucagon response to insulin hypoglycemia in control or diabetic rats. On the contrary, in control rats, the beta-adrenergic blocker alone or in combination with an alpha-adrenergic blocker and in diabetic rats, the alpha-adrenergic blocker alone significantly stimulated the glucagon response to insulin hypoglycemia. Second, the effects of yohimbine on the glucagon response to epinephrine infusion were studied in both young and old rats. Recently, Cherksey et al. (Proc. Soc. Exp. Biol. Med. 1982; 171:196-200) have reported that the adrenergic receptors on rat pancreatic islet cells are of the alpha 2-subtype. Yohimbine (alpha 2-adrenergic blocker) completely blocked the glucagon response to epinephrine infusion in both young and old rats, but had no inhibitory effect on the glucagon response to insulin hypoglycemia in control and short-term diabetic rats. From these observations, it could be inferred that the lack of glucagon response to insulin hypoglycemia in long-term diabetic rats is unlikely to be explained by an impairment of an adrenergic function.