The DNA synthesis activities of hepatocytes in primary biliary cirrhosis (PBC) and other chronic liver diseases and control subjects were examined by staining proliferating cell nuclear antigen (PCNA) with anti-PCNA monoclonal antibody. The number of PCNA-positive cells (PCNA value) was significantly higher in PBC (375 +/- 281 parts per thousand; ppt) than in other chronic liver diseases, i.e., chronic hepatitis (95 +/- 83 ppt), liver cirrhosis (72 +/- 71 ppt), and alcoholic liver disease (73 +/- 56 ppt), and in control subjects (11 +/- 14 ppt). The PCNA value of PBC in stages I-III of Scheuer's classification was remarkably high, while in stage IV it was low. Even in identical, Scheuer's stages, the PCNA value of PBC was higher in patients who were not given ursodeoxycholic acid (UDCA) than in those who received UDCA. In identical patients, the PCNA value was lowered significantly after UDCA treatment. It was concluded that the DNA synthesis activity of PBC in stages I-III was accelerated and that UDCA can alleviate the abnormality in DNA synthesis activity.