Serum free proline and free hydroxyproline were determined in 71 patients with liver disease and in 62 control subjects. The group with liver disease included 60 patients with liver cirrhosis and 11 with chronic active liver disease. Forty-five of the cirrhotic patients were alcoholics, 9 of which were studied during an episode of alcoholic hepatitis. The control group consisted of 24 healthy volunteers, 19 primary malnourished patients, and 19 severely ill patients without liver disease. The values obtained in normal subjects were quite constant; no differences related to sex or age were detected. In patients with malnutrition, and especially in severely ill patients, the proline values were always below the normal limit. Patients with nonalcoholic cirrhosis or chronic active liver disease had serum proline and hydroxyproline values similar to those of normal subjects. However, the patients with alcoholic liver cirrhosis had proline and hydroxyproline values significantly higher than the normal group. Furthermore, in patients with alcoholic hepatitis the serum free proline values were significantly higher than in the other groups. The results suggest that alcohol might have a direct effect on proline metabolism or facilitate its release from the liver cell.