To assess the effect of each dietary caloric source on the catabolism of branched-chain amino acids, we investigated the rate of leucine oxidation before and after obese volunteers consumed one of the following diets for one week: (a) starvation, Starvation significantly increased the rate of leucine oxidation (1.4±0.11 vs. 1.8±0.16 mmol/h, P < 0.01). The same occurred with the fat and protein diets. In sharp contrast, the 500-cal carbohydrate diet significantly decreased the rate of leucine oxidation (13±0.13 vs. 0.6±0.09 mmol/h, P < 0.01). The same occurred when a portion of the carbohydrate diet was isocalorically replaced with either fat or protein. The cumulative nitrogen excretion during the fat diet and starvation was not significantly different. As compared with the fat diets, the carbohydrate diets on the average reduced the urinary nitrogen excretion by 12 g/wk. Nitrogen balance was positive during the consumption of the 500-cal protein diet, but negative during the consumption of carbohydrate-protein diet. The fat diets, like the protein diets and starvation, greatly increased plasma leucine (119±13 vs. 222±15 uM, P < 0.01) and 0-hydroxybutyrate (0.12+0.02 vs. 4.08±0A3 mM, P < 0.01) concentrations, and significantly decreased plasma glucose (96±4 vs. 66±3 mg/dl, P < 0.01) and insulin (18±4 vs. 9±1 MU/nl, P < 0.05) concentrations. These changes did not occur, or were greatly attenuated, when subjects consumed carbohydrate alone or in combination with fat or protein.We conclude that (a) during brief caloric restriction, dietary lipid and protein, unlike carbohydrate, do not diminish the catabolism of branched-chain amino acids and (b) the decrease in branched-chain amino acid oxidation is associated with protein sparing.