The adrenergic modulation of immunoreactive insulin (IRI) and glucagon (IRG) secretion was studied in 5 massively obese subjects hospitalized ion a metabolic ward. Epinephrine was infused alone or in combination with propranolol, a beta adrenergic blocking drug, or with phentolamine, an alpha adrenergic blocking drug. Epinephrine infusion produced a significant (p less than .02) rise in IRG levels which was blocked by addition of either phentolamine or propranolol. Pure alpha adrenergic stimulation with propranolol-epinephrine infusion inhibited IRG secretion (p less than .02). IRI levels decreased with propranolol-epinephrine infusion (p less than .02), increased with phentolamine-epinephrine infusion, and were not affected by infusion of epinephrine alone. Glucose concentrations rose with all 3 infusions but were less with phentolamine-epinephrine. A control group of 4 lean outpatients on a ad lib diet demonstrated a similar pattern but the changes of IRG secretion were smaller than in the obese subjects and were not statistically significant. We conclude that in obese humans IRI secretion is increased by beta adrenergic stimulation, is decreased by alpha adrenergic stimulation, and is unaffected by combined alpha and beta adrenergic stimulation. In contrast, IRG secretion is stimulated by combined alpha and beta adrenergic stimulation, is inhibited by pure alpha adrenergic stimulation, and is unaffected by pure beta adrenergic stimulation.