To elucidate the status of serum hepatitis B virus (HBV) DNA in HBsAg-positive hepatocellular carcinoma (HCC), 100 type B chronic liver disease (CLD) patients and 19 HCC patients were studied. The positive rate of serum HBV DNA in HBeAg-positive CLD patients was significantly higher than that in HBeAg-negative CLD patients, and the correlation between the presence of serum HBV DNA and patients' age showed a negative trend. In contrast, the positive rates of serum HBV DNA in HCC patients were not related to the status of HBeAg and age, and the positive rate of serum HBV DNA in HBeAg-negative HCC patients was significantly higher than that in HBeAg-negative CLD patients. Nevertheless, the serum concentrations of HBV DNA in HCC patients were significantly lower than those in CLD patients. These results suggest that replication of HBV in HCC patients might differ from that in CLD patients, and that persistent low-level HBV replication might be related to the presence of HCC.