Muscarinic blockade by atropine has been shown to decrease the thermic effect of a mixed meal, but not of intravenous glucose. To further delineate the mechanisms involved in the atropine-induced inhibition of thermogenesis after a meal, plasma substrate and hormone concentrations, energy expenditure (EE) and substrate oxidation rates were measured before and during a continuous glucose infusion (44.4 mumol.kg-1.min-1) with or without atropine. After 2 h of glucose infusion, a 20-g oral fructose load was administered while the glucose infusion was continued. Plasma insulin concentrations attained a plateau at 596 (SEM 100) pmol.l-1 after 120 min of glucose infusion and were not affected by muscarinic blockade; plasma glucose concentrations peaked at 13.3 (SEM 0.5) mmol.l-1 at 90 min and decreased progressively thereafter; no difference was observed with or without atropine. Plasma free fatty acid and glucagon concentrations, with or without atropine, were both decreased to 201 (SEM 18) mumol.l-1 and 74 (SEM 4) ng.l-1, respectively, after 2 h of glucose infusion, and were not further suppressed after oral fructose. Carbohydrate oxidation rates (CHO(ox)) increased to 20.8 (SEM 1.4) mumol.kg-1.min-1 and lipid oxidation rates (Lox) decreased to 1.5 (SEM 0.3) mumol.kg-1.min-1 between 90 and 120 min after the beginning of glucose infusion and were not affected by atropine. Glucose-induced thermogenesis was similar with [6.5% (SEM 1.4%) of basal EE] or without [6.0% (SEM 1.0%), NS) muscarinic blockade during the 30 min preceding fructose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)