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 less than 0.001) with albumin, t1/2 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 less than 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.