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 nutrition or other therapeutical endeavors. Since free glutamine is unstable in solutions, the question is whether maintenance of this pool and improvement of the nitrogen economy is feasible by intravenous provision of synthetic, stable glutamine-containing dipeptides. In vivo studies in man and animals provide firm evidence that a synthetic glutamine containing dipeptide, L-alanyl-L-glutamine (Ala-Gln), is readily hydrolyzed following intravenous administration. The results also indicate a safe and efficient use of Ala-Gln as a source of free glutamine for parenteral nutrition. In clinical studies, nitrogen balance was more positive in catabolic patients receiving a peptide supplemented solution as compared with control patients given isonitrogenous, isoenergetic TPN. Preoperative muscle glutamine concentrations were essentially maintained in the peptide group and markedly decreased in the control group. It is inferred that the increased intestinal requirement of 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, to preserve the muscle glutamine pool, and to improve overall nitrogen economy during conditions of stress.