Of the total pool of muscle free intracellular amino acids, glutamine represents about 60%. During catabolic stress, a marked reduction (50%) of this pool occurs; the depletion is not reversible by therapeutic efforts or conventional nutritional means. If maintenance of the intracellular glutamine pool promotes conservation of muscle protein, there is a theoretical case for use of glutamine supplements in the parenteral nutrition of patients with injury and infection. Glutamine is too unstable and poorly soluble for addition to existing preparations in its native form, but this drawback can be overcome by the use of synthetic stable and highly soluble glutamine-containing dipeptides. In vivo studies in humans and animals provide firm evidence that a synthetic glutamine-containing dipeptide, L-alanyl-L-glutamine (Ala-Gln), is readily hydrolyzed following its intravenous administration. The results also indicate a safe and efficient use of Ala-Gln as a source of free glutamine in parenteral nutrition. In clinical studies, nitrogen balance was more positive in catabolic patients receiving a peptide-supplemented solution than in control patients given isonitrogenous, isoenergetic total parenteral nutrition. Muscle glutamine concentrations were markedly decreased in the control groups. The intracellular concentrations were not influenced following severe injury, but were maintained in postoperative trauma. It is inferred that the increased intestinal requirement and cellular demand for metabolic fuel during catabolic stress is matched by an enhanced demand on muscle glutamine, resulting in intracellular glutamine depletion. Thus, the delivery of adequate amounts of glutamine is essential to maintain the integrity of intestinal mucosa and rapidly proliferating cells, to preserve the muscle glutamine pool, and to improve overall nitrogen economy during conditions of stress.