Hepatitis C virus (HCV) infection prevalence was determined in 34 hepatocellular carcinoma (HCC) patients with underlying liver cirrhosis. Serum alfa-fetoprotein level was found to be more than 1000 ng/ml (3153 +/- 1451) in those patients. Anti-HCV antibodies were detected in 84% of patients sera negative for hepatitis B surface antigen (HBsAg), while HCV RNA was only detected in 28% of the sera of those patients. Schistosomiasis antibodies were found in 92% of the anti-HCV-positive HBsAg negative sera of HCC patients, while they were only detected in 61% of sera of control non HCC patients with anti-HCV antibodies and without HBsAg. HCV and hepatitis B virus (HBV) coinfection was found in 16% of the studied group, based on antibodies in sera, and in 9% based on the presence of HCV RNA. HBV (HBsAg) was found, on its own, in sera of 5.9% of the patients studied. These results show that HCV and schistosomiasis play a major role in the development of hepatocellular carcinoma in Egypt.