It has been suggested that glycosaminoglycans are involved in the pathogenesis of liver fibrosis. Furthermore, recent studies have reported that one of them, hyaluronate, was mainly taken up and degraded by the liver. Using an enzymoimmunological assay, based on hyaluronate-hyaluronectin interaction, serum levels of hyaluronate were measured in 113 patients with various liver diseases. Patients were divided into six groups according to clinical, biological and histological data: Group 1—alcoholic cirrhosis (n=47) including alcoholic cirrhosis with alcoholic hepatitis (n=24); Group 2—primary biliary cirrhosis (n=21); Group 3—cirrhosis related to viral hepatitis (n=10); Group 4—idiopathic hemochromatosis (n=17); Group 5—alcoholic fatty liver (n=8); and Group 6—viral or drug acute hepatitis (n=10). Ninety-four blood donors were studied as controls. Levels of hyaluronate were found to be strikingly elevated in Group 1 (1,225 ± 1,137 μg per liter), Group 2 (792 ± 739 μg per liter), Group 3 (649 ± 373 (μg per liter), and Group 4 (246 ± 242 μg per liter), whereas patients in Group 5 (94 ± 63 μg per liter) and Group 6 (73 ± 57 μg per liter) had values close to controls (23 ± 17 μg per liter). There was a significant correlation between serum hyaluronate and serum albumin, prothrombin time, factor V concentration and serum γ-globulins. It is suggested that hyaluronate levels reflect both active fibrosis and hepatic failure and may be a quantitative marker of severity of hepatic injury.