Objective To assess the efficacy of glutamine (Gin) dipeptide-enriched total parenteral nutrition (TPN) on selected metabolic, immunologic, and clinical variables in surgical patients. Summary Background Data Depletion of Gin stores might lead to severe clinical complications. Recent studies indicate that the parenteral provision of Gin or Gin-containing dipeptides improves nitrogen balance, maintains the intracellular Gin pool, preserves intestinal permeability and absorption, and shortens hospital stay. Methods Twenty-eight patients (age range, 42-85 years, mean 68 years) undergoing elective abdominal surgery were allocated, after randomization, to two groups to receive isonitrogenous (0.24 g nitrogen kg(-1) day(-1)) and isoenergetic (29 kcal/122 kJ kg(-1) day(-1)) TPN over 5 days. Controls received 1.5 g of amino acids kg(-1)day(-1), and the test group received 1.2 g of amino acids and 0.3 g of L-alanyl-L-glutamine (Ala-Gln) kg(-1)day(-1). Venous heparinized blood samples were obtained before surgery and on days 1, 3, and 8 after surgery for routine clinical chemistry and for the measurement of plasma free amino acids. Lymphocytes were counted and the generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes was analyzed before surgery and on days 1 and 6 after surgery. Nitrogen balances were calculated postoperatively on days 2, 3, 4, and 5. Results No side effects or complaints were noted. Patients receiving Gin dipeptide revealed improved nitrogen balances (cumulative balance over 5 days: -7.9 +/- 3.6 vs. -23.0 +/- 2.6 g nitrogen), improved lymphocyte recovery on day 6 (2.41 +/- 0.27 vs. 1.52 +/- 0.17 lymphocytes/nL) and improved generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes (25.7 +/- 4.89 vs. 5.03 +/- 3.11 ng/mL). Postoperative hospital stay was 6.2 days shorter in the dipeptide-supplemented group. Conclusion We confirm the beneficial effects of Gin dipeptide-supplemented TPN on nitrogen economy, maintenance of plasma Gin concentration, lymphocyte recovery, cysteinyl-leukotriene generation, and shortened hospital stay in surgical patients.