BACKGROUND We previously showed a decrease in ileal glutamine transport in vitro and net absorption in vivo after extrinsic denervation of the canine jejunoileum. The aim was to determine whether extrinsic innervation modulates in vivo net absorption and in vitro transport of glutamine and other nutrients in canine jejunum. METHODS In vivo net jejunal uptakes of glutamine, alanine, leucine, and glucose were measured in five dogs before and 2 and 8 weeks after a model neurally isolating in situ the jejunoileum (extrinsic denervation, intestinal transection). To assess mechanisms, carrier-mediated uptakes were quantitated in jejunal brush border membrane vesicles from six dogs before and at 2 and 8 weeks after neural isolation of the jejunoileum and compared with six control dogs with fully intact extrinsic innervation. RESULTS In vivo net absorption of glutamine decreased at 2 weeks (p < 0.05) and returned to normal values at 8 weeks; net absorptions of leucine, alanine, and glucose were decreased at both 2 and 8 weeks. In vitro brush border membrane vesicles transport of glutamine, leucine, and alanine followed the patterns of in vivo absorption, but glucose transport did not differ at any time point. Decreased glutamine uptake at 2 weeks resulted from a decrease in Vmax rather than a change in K(m) in sodium-dependent carrier-mediated transport. CONCLUSIONS Extrinsic denervation down-regulated carrier-mediated transport of amino acids but not glucose. Decreased in vitro glutamine transport was mediated in part by a decrease in number rather than affinity of sodium-dependent transporters.