This study describes and analyzes sequential changes in plasma and skeletal muscle free amino acids following severe burn injury. Plasma free amino acids were determined in children (n = 9) with burns averaging 60% total body surface area and were compared with laboratory beagles (n = 44) which received a flame burn totaling 30% of their body surface area. In addition, needle biopsy specimens were obtained from the semitendonosus muscle in the animals to determine free intracellular amino acids. In both patients and animals the amount of total free amino acids in plasma fell following burn, suggesting relative protein deficiency. This drop was primarily due to a 47% drop in nonessential amino acids. However, plasma phenylalanine was consistently higher than normal following burn, and was strongly associated with death and weight loss in both animals and patients, especially when analyzed as a ratio with tyrosine. This finding suggested excessive catabolism, hepatic dysfunction, or both. Plasma levels of several amino acids correlated significantly with weight loss. Alterations in muscle free amino acids generally were similar to plasma amino acids. Exceptions were muscle alanine and glycine which strongly correlated with weight loss. However, the determination of muscle free amino acid profiles did not yield clinically useful information not available from plasma profiles. Plasma levels of liver enzymes suggested progressive hepatic dysfunction. These studies show that the laboratory beagle is a good model for studying the metabolic alterations of amino acids that accompany burn injury, since they mimic humans in many parameters which appear to be most useful with respect to clinical evaluation.