To investigate the epidemiology of HCV in Taiwan, anti-HCV was studied by radioimmunoassay or enzyme immunoassay in patients with chronic liver disease, healthy adults, and subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs and 81% in 58 parenteral drug abusers. Anti-HCV was present in 6 (7.7%) of 78 HBsAg-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of 24 HBsAg-negative patients with HCC. An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to be positive for anti-HCV. In a prospective study of PTH, 37 or 13% patients contracted hepatitis and 22 (60%) were due to HCV, and at least 17 (77%) of them became chronic. Cloning of HCV genome in a Taiwanese patient with acute posttransfusion non-A, non-B hepatitis by using reverse transcription polymerase chain reaction was performed, and partial characterization of the nucleotide sequences showed 80% and 92% homology as compared to HCV sequences from Chiron and one of the published Japanese isolates, respectively. It is concluded that HCV infection plays a relatively minor role in HBsAg-positive liver decrease in Taiwan, but is strongly associated with HBsAg-negative chronic liver disease and HCC. It is also important in PTH, and the infection is extremely common in hemophiliacs and parenteral drug abusers. The Taiwanese strain of HCV seems more similar to that from Japan, as revealed by nucleotide sequences.