Oral rehydration therapy of diarrhea is based upon the promoting effect of glucose on sodium absorption. This ionic transport could be further enhanced by the addition of glutamine, an amino acid which is also the major energy source for the enterocyte. The aim of this in vitro study was to assess glutamine intestinal transport and to evaluate ionic movements associated with this transport. Strips of ileal epithelium from rabbits at weaning were mounted in Ussing chambers. Both sides of the epithelium were bathed with Ringer solution supplemented, after a basal period, with 2, 5, 10 or 25 mM glutamine. Unidirectional transepithelial fluxes of glutamine were measured with 3H and 14C tracers. Short circuit current, reflecting ionic transport, and potential difference were continuously monitored. Glucose 9 mM was later added to both sides. An apparent bidirectionnal transepithelial transport of glutamine was observed. The net result was a dose-dependent absorption (1.8 +/- 0.3 mumoles/h. cm2 at 25 mM). Glutamine induced a significant (p less than 0.01) dose-dependent saturable increase of short-circuit current and potential difference; the epithelial conductance was not modified. The addition of glucose did not significantly modify glutamine transport but caused and additional increase of short-circuit current. These results suggest that glutamine is actively transported by the ileal epithelium and stimulates ionic transport, suggesting Na+ absorption. The mechanism of this stimulation may differ from that of glucose, as the effects were additive. The present data provide support to the clinical evaluation of glutamine-supplemented rehydration solutions in the treatment of diarrhea.