OBJECTIVE To determine the possible role of adrenergic mechanisms in mediating the fall in serum potassium concentration after intravenous injection of insulin. METHODS Eighteen nondiabetic male volunteers, divided into three groups of six subjects, comprised the study. Hypoglycemia was induced by a bolus of short-acting insulin (0.15 U/kg body wt). Six subjects were studied in control conditions, six during alpha-adrenergic blockade with phentolamine, and six during beta-adrenergic blockade with propranolol. RESULTS In the control group, there was an immediate fall in serum potassium from 4.0 +/- 0.1 to 3.6 +/- 0.1 mM at baseline + 15 min. After the onset of acute hypoglycemia, potassium decreased further in the control group, reaching a lowest concentration of 3.3 +/- 0.1 mM. In the propranolol group, the late decrease in potassium was inhibited, and there were no further changes in serum potassium. During alpha-blockade, there was an exaggerated fall to 2.6 +/- 0.1 mM at 30 min after the onset of hypoglycemia. CONCLUSIONS The later fall in serum potassium, which occurs after the onset of hypoglycemia, is probably mediated by stimulation of beta-adrenoreceptors, whereas coincidental stimulation of alpha-adrenoreceptors opposes this fall in potassium and may prevent the development of severe hypokalemia in response to acute hypoglycemia.