A prospective clinical trial was undertaken to determine the nitrogen-sparing efficacy of three amino acid solutions with different concentrations of branched-chain amino acids (BCAA) in 25 postoperative patients. The patients were a homogenous male population with stage I bladder cancer who underwent radical cystectomy. Administration rates of the intravenous solutions were designed to provide 30 kcal/kg/day and 1.5 g protein per kg per day during the 7-day study period. A control group (n = 4) received 5% dextrose in water (150 g/day). Nitrogen balance was determined daily and the whole body protein turnover was measured using a primed-constant infusion of 15N glycine on postoperative days 3 and 4. The group receiving the 45% BCAA enriched (low leucine) amino acid solution exhibited a significant decrease in cumulative (7 day) nitrogen balance (7.6 +/- 2.6 g) compared to the groups receiving either the standard 25% BCAA (19.9 +/- 2.1 g) or the 45% BCAA enriched (high leucine) (21.6 +/- 7.0 g) amino acid solution. The group receiving the 45% BCAA enriched (low leucine) amino acid solution exhibited a higher rate of mean whole body protein catabolism compared to the other groups. For patients undergoing major elective operations, the amount of leucine necessary for optimal daily nitrogen balance was 0.13 g/kg/day. These results demonstrate that the ratio of individual BCAA and the amount of leucine were more critical to nitrogen-sparing efficacy than the percentage total BCAA infused.