To investigate the effect of the autonomic nervous system on the thermic response to food ingestion, respiratory exchange measurements were performed on seven healthy young men for 1 h and 45 min before and 6 h after ingestion of a mixed meal, approximately 560 kcal, 53% carbohydrate, 30% fat, and 17% protein (control) and under the same conditions during infusion of either propranolol (80 micrograms/kg bolus and 1 microgram.kg-1.min-1), atropine (10 micrograms/kg and 10 micrograms.kg-1.min-1), or atropine plus propranolol. The postabsorptive resting metabolic rates were the same on each occasion and were slightly altered by drug treatment. The thermic responses to the meal were the same with the control and propranolol tests (9.3 +/- 0.9 and 9.2 +/- 0.5%, respectively) and were greater (P less than 0.001) than with atropine 3.6 +/- 0.6% and atropine plus propranolol 3.3 +/- 0.8%. Blockade of the sympathetic nervous system does not decrease the thermic response to food taken orally, whereas muscarinic receptor blockade does. Although some confounding effects of atropine might explain some of this decrease, our results suggest that the parasympathetic nervous system is involved in the thermic effect of food.