The effect of different intravenous nutritional regimens on nitrogen balance and 3-methylhistidine (3-MeHIS) excretion were studied during a 6-day period following major elective surgery in 28 patients. All patients were kept on a synthetic diet 4 days prior to surgery and were given 0.1 g amino acid N and 120 kJ/kg . day. Postoperatively, all patients received parenteral nutrition with approximately 170 kJ/kg . day. Postoperatively, all patients received parenteral nutrition with approximately 170 kJ/kg . day. Three groups of patients were given varying amounts and proportions of amino acids while in one group no amino acids were administered. Preoperatively, urinary 3-MeHIS excretion (determined by a newly developed automatic analyzer) was 240.3 mumole/day +/- 9.2, nitrogen balance was -1.8 g N +/- 0.19. Postoperatively, nitrogen balance was less negative when amino acids were given. The degree of improvement depended on the amount, but not on the composition of nitrogen administered. In all four groups, 3-MeHIS outputs were elevated when compared with preoperative excretion. The 3-MeHIS excretion (mumole/day) was increased more in patients on high amino acid supply than in patients with low or no nitrogen supply. In each of the groups the 3-MeHIS excretion was negatively correlated to the nitrogen balance. Regression analyses suggest that postoperative muscle protein breakdown occurs in relation to the body protein loss. Amino acid administration seems not to decrease muscle protein breakdown, but rather, appears to stimulate protein synthesis, resulting in less net protein loss. The mean rate of muscle protein breakdown in the postoperative state was estimated to be 80 g/day, assuming 4.2 mumole 3-MeHIS per g mixed human muscle protein. This exceeded the mean preoperative breakdown by about 23 g muscle protein per day. This increase might be due to the metabolic response to the trauma and also in part to tissue damage by the surgical procedure.