In seven healthy male subjects, intake of 100 g protein hydrolysate produced significantly greater increments in energy expenditure than intake of 100 g glucose, 44 g fat, or a noncaloric control solution during the first 4 hr postcibum. Glucose and fat intake produced similar increments in energy expenditure. In contrast to the effects on thermogenesis, protein and fat intake did not alter sympathetic nervous system (SNS) activity, as estimated by plasma norepinephrine (NE) levels, whereas glucose intake significantly increased NE levels. Plasma levels of immunoreactive insulin were stimulated by glucose intake to a much greater level than by protein intake, and were unaffected by ingestion of the fat and control solutions. Pulse rate significantly increased following ingestion of all nutrients compared to pulse rate changes during the control test. These data support the traditional concept of a greater thermic effect of protein than of carbohydrate or fat, but the possibility of SNS involvement in the thermic effect of protein and fat is not supported.