The role of beta-adrenergically mediated sympathetic nervous activity in the regulation of glucose-induced thermogenesis was examined in healthy male subjects. Respiratory gas exchange was measured continuously, using the ventilated hood technique, under conditions of hyperinsulinemia and hyperglycemia (glucose clamp technique, insulin infusion 1 mU/kg per min, glucose levels 125 mg/dl above basal) before and after beta-adrenergic blockade (i.v. propranolol, 3-mg bolus plus 0.1 mg/min for 2 h). After 2 h of insulin and glucose infusion in series 1, glucose uptake had increased to 23.5 +/- 2.3 mg/kg per min and insulin concentration to 199 +/- 21 microU/ml. Simultaneously, the energy expenditure had risen by 0.39 +/- 0.05 kcal/min above basal. After propranolol administration, glucose uptake did not change, while energy expenditure fell significantly, to a level 0.28 +/- 0.04 kcal/min above basal. The glucose-induced thermogenesis (GIT) was 6.5 +/- 0.3% before and 4.6 +/- 0.5% (P less than 0.02) after propranolol. In series 2, insulin and glucose infusion was continued for 4 h without propranolol administration. Glucose uptake rose (+12%) and insulin levels increased (+40%) between the 2nd and 4th h but energy expenditure and GIT remained unchanged. Subjects in series 3 received saline infusion alone for 3 h, at which time propranolol administration as in series 1 was added during a further 2-h period. No changes in energy expenditure were seen during saline or propranolol infusion. These data demonstrate the presence of a beta-adrenergically mediated sympathetic nervous component in glucose-induced thermogenesis in healthy human subjects. This factor may be of importance in the regulation of normal body weight in man.