A 60-year-old woman with chronic active hepatitis C was treated with 6 million units of rIFN-alpha 2b daily for two weeks and subsequently three times weekly for several months. Histological examination proved a severe form of chronic active hepatitis C unexpectedly complicated with primary biliary cirrhosis (PBC). Before treatment, levels of serum alkaline phosphatase (ALP) or gammaglutamyltranspeptidase (GGT) had remained within normal limits over six months, although anti-mitochondrial antibody (AMA) was shown to be positive. After eight weeks of therapy, the daily dose of rIFN was reduced to 3 million units because of a marked increase of ALP and GGT, although the serum alanine aminotransferase (ALT) was normalized. Four months later, IFN treatment was suspended because of continuous elevation of the ALP and GGT levels, and administration of ursodeoxycholic acid was substituted. Two months later, the ALP and GGT levels returned to the normal range, although ALT was not normalized and HCV-RNA remained positive. This is the first report case that demonstrates IFN treatment potentially exacerbates PBC associated with chronic active hepatitis C. It is important for treating physicians to keep this association in mind.