A hepatitis C virus (HCV) chronically infected patient developed an episode of acute hepatitis during the course of immunosuppressive therapy given for a lymphoproliferative disease. It was noted that anti-HCV antibody response, seen to be relatively stable during the follow-up, lowered dramatically in coincidence with the hepatocytolytic peak. A diagnostic liver biopsy taken at the time of the acute phase of hepatitis demonstrated a typical feature of lobular hepatitis with widespread lymphocytic infiltrates, the predominant type of which expressed CD8 immunophenotype. Cytotoxic and immunosuppressive drugs may interfere with hepatitis virus infections. However, at variance from hepatitis B virus infection in which acute liver decompensation develops after withdrawal of chemotherapy in our HCV chronically infected patient it appeared during the course of the treatment, suggesting a different hepatocytolytic mechanism. Although the actual frequency of the phenomenon is presently unknown, this observation seems to indicate that immunosuppressive and cytotoxic agents should be used with caution in HCV chronic infection in which cell-mediated immune response seems to play a major role in the production of the liver damage.