A total of 29 patients with well-compensated alcoholic cirrhosis and 9 healthy control subjects of similar age and sex were studied to assess their response to a challenge of 2 L of normal saline infused over a 1 hr period. Patients with cirrhosis had an adequate effective arterial blood volume in the basal state as assessed by neurohumoral markers of vascular filling. They also had a lower renal vascular resistance (p = 0.048) and a higher glomerular filtration rate (p = 0.014) than the controls, indicating the presence of renal vasodilation. Both groups were in sodium balance, but the patients with cirrhosis had a higher filtered load of sodium, an increased proximal tubular reabsorption of sodium (p = 0.015) and a decreased fractional excretion of sodium (p < 0.001). The administration of a saline load was not accompanied by any significant changes in the renal circulation in the patients with cirrhosis. They were unable to suppress their proximal tubular reabsorption of sodium to the same extent as the controls (p = 0.012), so by the fourth hour a significant difference in the rate of urinary excretion of sodium was evident. In the patients with cirrhosis, glomerular filtration rate before and after the saline load correlated significantly with indocyanine green extraction (r = 0.65; p = 0.002), whereas the tubular handling of sodium was dependent on antipyrine clearance (r = 0.80; p < 0.001). The results indicate that in well-compensated alcoholic cirrhosis, abnormalities in the renal circulation and tubular handling of sodium occur before evidence exists of a decreased effective arterial blood volume and are independent, with the renal vasodilatation being related to the extent of intrahepatic shunting, whereas impaired renal tubular sodium handling is dependent on hepatic function. These results are consistent with the hypothesis that, in cirrhosis, activation of neurohumoral pressor systems is not solely responsible for the changes in sodium homeostasis that predispose to the development of ascites. (Hepatology 1994;20:873–881).