BACKGROUND/AIMS Glutamine (Gln) is considered a trophic factor for small intestinal epithelia, which is important during severe illness. Its use in parenteral nutrition is precluded by its instability, a problem that may be overcome by use of the stable dipeptide L-alanyl-L-glutamine (Ala-Gln). The hypothesis was tested that Gln or Ala-Gln may stimulate cell proliferation not only in the ileum but also in the proximal and distal colon and, thus, may contribute to the gut barrier function. METHODS Biopsy samples from the normal human ileum, proximal colon, and rectosigmoid were incubated for 4 hours with Gln (2 mmol/L), Ala-Gln (2 mmol/L), and saline (control). Cells in S phase were labeled with bromodeoxyuridine. In longitudinal crypt sections labeled and quiescent cells were counted. RESULTS Gln as well as Ala-Gln stimulated crypt cell proliferation in the ileum, proximal colon, and rectosigmoid colon. In ileal specimens, labeling was greater in the entire crypt, whereas in both colonic regions, the trophic effect was confined to the basal crypt compartments. CONCLUSIONS Gln and Ala-Gln have trophic effects not only in the ileum, but also in the proximal and distal colon. This could be important during parenteral nutrition when mucosal atrophy may weaken the gut barrier.