Increasing evidence suggests that glutamine is important for the function of many organ systems and supports the use of glutamine-enriched total parenteral nutrition (TPN) during severe illness. However, the effect of prolonged glutamine supplementation on glutamine kinetics has not been studied.We investigated the effect of 8-10 d of TPN enriched with glutamine dipeptides on glutamine kinetics.Twenty-three preoperative patients were randomly allocated to receive either TPN enriched with glutamine dipeptides (60 micromol glutamine*kg body wt(-1)*h(-1)) or isonitrogenous, isoenergetic, glutamine-free TPN. A primed, continuous, 6-h intravenous infusion of L-[5-(15)N]glutamine and L-[1-(13)C]leucine was given before (baseline) and 8-10 d after the TPN solutions were administered. Baseline measurements were performed after a 40-h administration of a standard solution of glucose and amino acids (no glutamine).Glutamine-enriched TPN increased the total appearance rate of glutamine (P: <0.05) but did not inhibit or increase the endogenous appearance rate. The standard TPN solution also increased the glutamine appearance rate (P: <0.05), but the change was much smaller than in the glutamine-supplemented group (P: <0.01). The plasma glutamine concentration did not rise significantly during either treatment, suggesting increased tissue glutamine utilization, especially in the glutamine-supplemented group.In view of the enhanced glutamine requirements in response to trauma and disease by tissues such as those of the gut, the immune system, and the liver, increased glutamine availability during glutamine-enriched TPN may be beneficial preoperatively in patients with gastrointestinal disease.