The presence of hepatitis C virus (HCV) RNA in serum and liver tissue was examined in seven patients with hepatocellular carcinoma (HCC), using the reverse transcriptase-polymerase chain reaction method with primers for the 5'-noncoding region. Plus-strand HCV-RNA was detected in the serum and liver tissue (both cancerous and noncancerous tissue) of all five patients who were positive for anti-HCV antibodies (C100-3 and P22) and was not detected in both of two patients who were negative for anti-HCV antibodies. Minus-strand HCV-RNA was only detected in the liver tissue (cancerous and noncancerous portion) of the five anti-HCV antibody-positive patients. The relative liver tissue content of minus-strand HCV-RNA ranged from 1 to 100 time less than that of plus strand HCV-RNA in cancerous and noncancerous tissue in each patient, respectively. There was no similar tendency in the HCV-RNA content between the cancerous and noncancerous portions of the liver in each patient. These results suggest that HCV exists and replicates in HCC tissue and may have some role in the development of HCC.