A prospective, randomized, double-blind trial of nutritional effects of branched chain modified amino acid solutions was undertaken in 23 surgical patients within 24 hours of the onset of major general surgery, polytrauma, or sepsis. The effects were evaluated in the absence of abnormalities of oxygen transport and perfusion in an isocaloric/isonitrogenous setting where the major difference between the groups was the amount of branched chain amino acids received. Both groups received balanced parenteral nutrition with 1.5 gm/kg/day of amino acids, 30 calories/kg/day of glucose, and 7 calories/kg/day of fat. At the end of the 7-day study interval, the group receiving the branched chain enriched therapy at 0.7 gm/kg/day of branched chain amino acids had improved nitrogen retention; an elevation of their absolute lymphocyte count from 800 to 1800/mm3, a reversal of anergy to recall skin test antigens in 60% of the patients, and improved plasma transferrin levels (p<0.03). Nutritional support using the modified amino acid metabolic support solutions has beneficial effects during the stress interval that do not seem as achievable with current commercially available nutritional support regimens.