To determine any potential benefit of feeding increased amounts of protein to hypermetbolic burned patients, 18 children with burns averaging 60% total surface area were randomized into two matched groups and studied serially for at least six weeks: the first group was given a normal diet with a balanced nutritional supplement, and the second group was supplemented with milk whey protein. The normal protein group received 87.1% of their desired caloric intake with 16.5% of calories from protein compared to 77.7% of desired caloric intake with 23.0% of calories from protein for the high protein group. Despite a higher caloric intake, the normal protein group had a worse opsonic index compared to the high protein group (0.42 +/- 0.04 vs. 0.62 +/- 0.05, p < 0.0007), lower levels of C3 (1371 +/- 55 vs. 1585 +/- 64 micrograms/ml, p < 0.01), lower levels of IgG (805 +/- 52 vs. 975 +/- 56 micrograms/ml, p < 0.03), lower levels of transferrin (200 +/- 10 vs. 283 +/- 18 mg/dl, p < 0.0001), lower levels of total serum protein (5.5 +/- 0.1 vs. 6.3 +/- 0.2 g/dl, p < 0.005), more bacteremic days (11% vs. 8%, p < 0.005) and worse survival (5/9--56% vs. 9/9--100%, p < 0.03). Patients receiving the high protein diet had significantly higher plasma levels of valine, lysine, threonine, leucine, aginine, isoleucine, proline, serine, asparagine, tryptophane, and tyrosine. Asparagine levels were significantly (p < 0.01) associated with better neutrophil function and opsonic index. Except for phenylalanine, significant associations were found for serum levels of each of the amino acids with concentrations of one or more serum proteins. These studies provide evidence that many immunologic functions are dependent upon optimal availability of specific amino acids, and that routine diets do not provide sufficient protein to satisfy the needs of seriously burned children.