Meal-stimulated colonic absorption has recently been described, but the cellular transport mechanisms mediating this response are unknown. The purpose of this study was to determine the contribution of Na+ transport pathways to colonic proabsorption. Distal colonic Thiry-Vella loops were constructed in six dogs. Absorption was measured by infusing the loops with a physiological electrolyte solution containing [14C] polyethylene glycol as the impermeant marker. In the first set of experiments, the dose dependence of amiloride-induced inhibition of basal colonic absorption was determined. In the second set of experiments the effect of amiloride, which inhibits both Na+ channels and Na+/H+ exchange in colonocytes, on meal-stimulated colonic absorption was determined. Luminal amiloride inhibited basal colonic absorption in a dose-dependent manner, with significant reductions in Na+ absorption occurring with concentrations of 10(-2)M and higher. Infusion with 10(-3)M amiloride, a concentration that did not alter basal absorption, resulted in significant reductions in postprandial water, Na+, and Cl- absorption. These results suggest that meal-stimulated colonic absorption is mediated, at last in part, by transcellular Na+ absorptive pathways.