To investigate the prevalence of point mutation in the pre-core (pre-C) region of hepatitis B virus (HBV) DNA, we performed dot blot hybridization and sequencing of enzymatically amplified HBV DNA from the sera of 25 patients with HBeAg-positive and 32 patients with HBeAg-negative chronic liver diseases. The pre-C region of HBV DNA was successfully amplified by polymerase chain reaction (PCR) from 55 (96.5%) of 57 sera. According to the status of serum HBeAg, HBV DNA was amplified from all 25 sera of HBeAg-positive patients and 30 (93.8%) of 32 sera of HBeAg-negative patients. All amplified DNA from the sera of 25 patients with HBeAg-positive and that from 28 (93.3%) of 30 patients with HBeAg-negative chronic liver diseases hybridized with the wild type probe. In addition, that from 5 (20.0%) among 25 patients with HBeAg-positive and 16 (53.3%) among 30 patients with HBeAg-negative chronic liver diseases hybridized also with the mutant type probe. These results suggest that the prevalence of point mutation in the pre-C region of HBV DNA is relatively high in patients with HBeAg-negative chronic liver diseases and further study is mandatory to identify the significance of this mutation.