To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the severity of primary biliary cirrhosis, a long-term prospective open trial in 54 consecutive PBC patients, 19 with histological stage I-II, 24 stage III, and 11 stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT, bilirubin) were done initially and every six months. Serum hyaluronate (HY) and type III procollagen amino propeptide (PIIIP) were also evaluated, as they are considered markers of fibrosis and prognosis. All patients were followed-up for at least two years (24-36 months); results were analyzed at 24 months after treatment. The composite pruritus score failed to show significant changes during UDCA treatment, while intensity score demonstrated a significant reduction from the 6th month. Patients with histological stage I-II disease had a significant decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months and maintained the levels up to 24 months. The patients with histological stage III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but not GGT) up to month 18; subsequently AST and ALT serum levels increased, reaching values comparable to baseline by 24 months. In patients with histological stage IV disease no significant change in liver enzymes was observed during the follow-up. HY and PIIIP serum levels failed to show significant changes during UDCA treatment in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)