Plasma volume was measured by using albumin-(131)I- and (51)Cr-labeled erythrocytes in 24 control subjects, 140 patients with hepatic cirrhosis, and 10 patients with various portal-systemic shunts for the relief of noncirrhotic portal hypertension. The cirrhotic patients included subgroups with ascites, functional renal failure, and portacaval anastomoses. Elevated values for plasma volume, by both methods, were found in each group of patients.The lymph space drained by the thoracic duct was measured by a radioisotopic technique in six patients with cirrhosis and ascites. The amount of radioactivity in this space was found to be negligible in accounting for the elevated plasma volume. Similar results were obtained when the degree of leakage of albumin-(131)I into the ascites was determined in 10 patients with cirrhosis.The plasma volume was unusually elevated in patients who had bled from esophageal varices, and paired comparisons before and after portacaval shunt normal values. There was a statistically significant correlation between normal values. There was a statistically significant correlation between plasma volume and wedged hepatic venous pressure measured in 36 patients.We concluded that the elevated values for plasma volume in cirrhosis are valid and are not artifacts due to leakage of albumin-(131)I from the circulation during mixing. We also concluded that portal hypertension is responsible for the plasma volume expansion; however, we were unable on this basis to explain the failure of portacaval shunting to return the plasma volume to normal, unless the shunt or some other factor keeps the plasma volume elevated.