To evaluate serum hyaluronate as a marker for progressive liver injury in patients with primary biliary cirrhosis, a longitudinal study including 48 patients was conducted with a mean follow-up time of 40 months. The patients were examined every 6 months with a standardized set of conventional liver function tests, and a liver biopsy was performed every year. The hyaluronate concentration correlated significantly (p < 0.001) with albumin, t 1/2 galactose tolerance test, bilirubin and prothrombin time but not to serum variables reflecting inflammatory activity. Furthermore, there was a close correlation between serum hyaluronate levels and histopathological changes in the liver. The hyaluronate concentration increased significantly over time in all clinical stages of primary biliary cirrhosis (p < 0.01), whereas the conventional liver function tests only changed in the advanced cases. The present data indicate that serum hyaluronate may be a sensitive marker for progressive liver damage in primary biliary cirrhosis. Serial determinations of hyaluronate are therefore of potential value for monitoring liver function during clinical management of the condition.