A B S T R A C T Studies were performed in rat small intestine in vivo to determine the effect of saline infusion on intestinal transport of Na' and I-O. Saline infusion decreased net Na4 flux (J.Na) from 12.7 ±0.8 to 6.4 ±1.5 AEq/hr per cm in the jejunum when the intestinal perfusate contained both Na4 and glucose. A similar fall in JnNR occurred in ileum. When mannitol was substituted for glucose in the perfusate, control absorption decreased 29% in jejunum and 18% in ileum, but saline infusion still caused a decrease in J.Na quantitatively similar to that seen when glucose was present. When choline was substituted for Na' in the perfusate, there was net movement of Na4 from blood to lumen during control and this net secretion was increased further after saline infusion. These observations suggest that saline infusion has a similar effect to decrease intestinal JnNa under three widely different conditions of basal sodium transport. Permeability of intestinal mucosa to inulin was very low under basal conditions but increased fivefold after saline infusion, and the unidirectional flux of Na4 from blood to lumen doubled. This increase in unidirectional flux of Na' was greater than the observed decrease in Jn.. Thus, saline infusion decreased net absorption of Na4 and H2O from small intestine through mechanisms which did not appear to be dependent upon the rate of Na4 flux from lumen to blood, and in association with an increased flux of inulin and Na4 into the intestinal lumen. The data suggest that the effect of saline infusion to decrease net absorption from the intestine could be due either to an increase in passive permeability of the epithelium which could disrupt solute gradients within the membrane or to an increase in flow of solution into the intestinal lumen.