The aim of this study was to assess the independent effects of carbohydrate and protein intakes in protein sparing during weight reduction. Forty-eight obese women were randomly assigned to consume isoenergetic (2500 kJ/d) liquid diets that provided the following amounts (g/d) of protein and carbohydrate, respectively, for 28 d: 50 and 10, 50 and 76, 70 and 10, and 70 and 86. The effects of carbohydrate and protein were analyzed by repeated-measures analysis of variance (ANOVA). Carbohydrate significantly affected daily urinary ammonia and total nitrogen excretion, stool nitrogen, and nitrogen balance. Protein, independently of carbohydrate, significantly affected daily urinary ammonia, urea, and total nitrogen excretion but had no effect on nitrogen balance. Cumulative nitrogen losses (mmol/28 d) were lower in the high-carbohydrate groups than in the low-carbohydrate groups (1869 +/- 392 and 3611 +/- 328, P = 0.003) but were similar in the groups receiving 50 and 70 g protein/d (3171 +/- 327 and 2326 +/- 430, respectively, P = NS). These results indicate that carbohydrate and protein have independent but additive protein-sparing effects during weight reduction.