Overfeeding normal volunteers with either carbohydrate or a mixture of supplements for 20 days increased resting metabolic rate, but most of the excess energy was retained. There was no significant increase in urinary VMA or catecholamine excretion or plasma catecholamine concentrations during overfeeding, suggesting that there was no diffuse activation of the sympathetic nervous system. Overfeeding did not enhance the thermogenic response to norepinephrine infusion, suggesting that the increase in resting metabolic rate during overfeeding in man is not mediated by increased sensitivity to norepinephrine or by hypertrophy of brown fat. Propranolol slightly reduced postprandial resting metabolic rate during overfeeding is not mediated by increased sympathetic nervous system activity. These data are not consistent with the hypothesis that the sympathetic nervous system regulates dietary thermogenesis in man.