To evaluate the role of hepatitis C virus (HCV) in Chinese patients with hepatocellular carcinoma (HCC), the antibodies to HCV (anti-HCV) were detected by enzyme immunoassay in 41 (12.6%) of the 326 patients with HCC. However, none of 35 patients with metastatic carcinoma of the liver had detectable anti-HCV. The prevalence of anti-HCV was significantly higher in patients with hepatitis B surface antigen (HBsAg)-negative HCC than those with HBsAg-positive HCC (37.3% versus 4.1%, P less than 0.0001). However, the prevalence of anti-HCV was much higher in patients with HCC with negative results for HBsAg and antibody to hepatitis B core antigen (54.5%). The mean age of patients with HCC with positive results for anti-HCV was significantly greater than that of patients with HBsAg-positive HCC (65.1 versus 55.5 years, P less than 0.0001). Alpha-fetoprotein levels greater than 20 ng/ml were found in 70.7% of patients with HCC with positive results for anti-HCV and in 73.3% of patients with HBsAg-positive HCC. Of the Chinese patients with HCC, 74.5% had HBsAg-positive results and 96.6% had positive results for antibody to hepatitis core antigen. These data indicate that, although HCV may play an etiologic role in HCC, hepatitis B virus is still the most important causal agent among most Chinese patients with HCC.