Today's knowledge on the natural history of hepatitis C virus infection derives mainly from local outbreaks and still limited clinical trials. There is a general consensus now that chronic infection occurs in at least 80% of cases after acute disease. Chronic hepatitis C usually runs a mild course with little or no morbidity. In a 15-yr follow-up evaluation of a cohort of 152 women having been infected with HCV-contaminated Rho (D)-immunoglobulin none had developed chronic active hepatitis or cirrhosis. On the other hand, half of 80 patients who started out with more advanced forms of chronic hepatitis C developed cirrhosis over a mean period of 12 yr. Recent observations indicate that progression to severe chronic hepatitis may even occur in HCV-RNA positive individuals with normal aminotransferase activities in serum for long periods. Overall, chronic HCV infection is a slowly progressive disease which often needs histological evaluation, especially in patients with normal biochemical findings.