During the turmoil after the end of World War II some 50 years ago, in Japan intravenous methamphetamine was widespread and penetrated the young generation aged 15-25 years and remunerated blood donors. The vicious cycle gave an enormous thrust to the spread of hepatitis C virus (HCV) infection among drug users and blood donors. Their HCV infection was transmitted to the general population through transfusions, folk medicine involving the breaking of the integument and tattooing. Indiscreet and widespread treatment with intravenous injection using contaminated syringes and needles at that time accelerated the transmission of HCV further. An overall result was the outbreak of HCV infection in restricted subpopulations in Japan, which inevitably involved the general population. Abrogation of paid blood donation in 1968, the exclusion of blood units contaminated with hepatitis B virus (HBV) in 1973 and that of HCV since November 1989 (by the second generation tests after February 1992) decreased the risk of posttransfusion hepatitis from >50% in the 1960s to infinitely close to zero at present. Now the incidence of HCV infection in Japan is decreased to 1.8-3.5/100,000 person-years. Mother-to-baby transmission of HBV has been prevented since 1986 by a combined passive and active immunoprophylaxis of the babies at risk with hepatitis B immune globulin and vaccine. What we see today in Japan, however, is an ever-increasing incidence of hepatocellular carcinoma (HCC) that has reached almost 40/100,000 population, with males >50 years accounting for the great majority. Of the HCC cases in Japan, approximately 16% is caused by HBV infection and approximately 80% by HCV infection. The growing incidence of HCC is expected to reach a plateau around the year 2015, and then to start to decrease. The ordeal we have gone through, with special reference to the increasing incidence of HCV-associated HCC, is expected elsewhere in the world with a current profile of age-specific HCV infection like ours a few decades back. For worse or better (probably in this order), Japan is a country far advanced as regards the HCC associated with HCV infection. Our long-term experience related in detail here is hoped to help plan strategies to contain HCV infection and cope with its long-term sequelae in many other countries worldwide.