We previously reported that 1 week of propranolol treatment (160 to 240 mg/d, orally) reduced resting metabolic rate (RMR) an average of 9% in healthy men. To determine whether this response was caused by the 25% reduction in serum triidothyronine (T3), rather than beta-adrenergic blockade, we examined the effect of nadolol on RMR in five healthy men. Nadolol is a nonselective beta-adrenergic antagonist that does not affect T3 production. After 6 to 10 days of nadolol treatment (240 mg/d), mean postabsorptive RMR declined 7% (P less than .01), with no significant change in serum T3 or thyroxine (T4) concentrations. This effect is significantly different from that of a hospitalized control group that received no drug and had no change in mean RMR, and was not different from the response to propranolol (previously published data). Nadolol slightly reduced the mean thermic response to a meal (12%), but this effect was not statistically significant. Mean postprandial RMR was 8% lower after nadolol treatment (P less than .01), mainly because of the reduced postabsorptive RMR, rather than a change in the response to the meal. These data suggest that beta-adrenergic activity makes a small but significant contribution to resting energy expenditure in man.