China has not been extensively investigated for the prevalence of hepatitis C virus (HCV) infection among people with or without liver disease. We analyzed serum from 2,177 liver disease patients from 7 cities in different areas of China. Of 435 acute hepatitis patients, only 11% were positive for HCV RNA, while hepatitis B surface antigen (HBsAg) was detected in 33%. Of 1,668 patients with chronic liver disease, 14% and 74% were positive for HCV RNA and HBsAg, respectively. Nearly 80% of non-B chronic liver disease were negative for HCV RNA. The frequency of HCV RNA in chronic liver disease was significantly higher in Hami (32%) and Shenyang (30%) than in other cities (6-12%). The HCV genotype distribution varied by region. Genotype III was detected in 46-70% of HCV infections in Hami, Shenyang, and Lanzhou, while more than 90% of patients from southern cities (Nanjing, Nanning, and Chengdu) had genotype II. No evidence for genotype I or IV infections was found. A full-length HCV genome sequence (HC-C2) derived from a Beijing patient with genotype II was closely related to previous isolates from Japanese and Taiwanese patients. These results suggest that HCV prevalence and genotype distribution vary from region to region in China, and that the HCV now predominant in China may have evolved epidemiologically with infections in Japan and Taiwan. The study identified a high frequency of non-B, non-C chronic liver disease in China, suggesting possibly a new agent or infections with extreme variants of HCV.