Isotonic expansion of extracellular fluids diminishes the reabsorption of sodium in the proximal tubule. If this effect is mediated through some mechanism extrinsic to the kidney, net sodium flux in other epithelial structures, such as the jejunum, should also be influenced. In the rat, expansion of E.C.F. produces in all experiments a diminished reabsorption of sodium and water, which appears during the first period after the infusion of saline is started and becomes statistically significant in the following periods. Because of the experimental conditions, net fluxes are often nverted, giving rise to a secretion. At the same time, the sodium concentration of the solution perfused increases during its transit through the jejunum. Net potassium flux is unchanged. Aldosterone has no influence on the phenomenon whereas angiotensin may have an additive effect. A similar response of two epithelial structures as far apart as the jejunum and the proximal tubule is highly suggestive of a common mechanism extrinsic to the kidney. The experimental model chosen has excluded the role of a suppression of aldosterone and angiotensin. There is lso no support for the involvement of a sodium-potassium exchange system. The present model offers the opportunity to study without any major technical problem the possible role of general, humoral and physical factors, all of which have been proposed as responsible for the diminished reabsorption of sodium in the proximal tubule after E.C.F. expansion.