The involvement of the liver in the control of the renal excretion of water and sodium can be deduced from some recent investigations. Hypertonic or isotonic sodium chloride infusion into the hepatic portal vein enhanced renal sodium excretion when compared with identical infusions into a systemic vein. It has been suggested that a humoral factor produced by the liver could be a functional link between the liver and the kidney. In order to test this hypothesis, the present experiments were carried out in two groups of anesthetized dogs. Animals from group I were infused with NaCl (855 mmol/l) at a rate of 0.05 ml/min/kg b.w. during 30 min, into the portal vein. Blood samples were withdrawn from the suprahepatic vein, before (SH1) and coinciding with the maximal natriuresis after hypertonic saline infusion (SH2). Plasma from SH1 and SH2 were infused into the left renal artery (LRA) of dogs from group II. Two 20 min clearance periods were performed before and after each SH-infusion. After both SH-infusions urinary sodium excretion (UNaV) was significantly increased from preinfusion values in both kidneys, and these increases were significantly greater after SH2 than after SH1. No significant differences were found in UNaV between left and right kidney. After both plasma infusions the increases in urinary volume and osmolar clearance were higher in the infused than in the not infused kidney. These results suggest that the plasma leaving the liver contains a substance with natriuretic activity and that the infusion of hypertonic NaCl into the portal vein could induce either a higher secretion of the same substance or the presence of other different substance.