Recently, an association between hepatitis B virus (HBV) genotype and clinical characteristics has been identified. Of special interest is the recent increase of acute hepatitis B (AHB) genotype A observed in urban areas of Japan. To determine the clinical characteristics associated with AHB genotype A, we compared admission serum levels of alanine aminotransferase, total bilirubin, and HBV markers for patients infected with AHB genotype A (A group) and AHB genotypes B or C (non-A group). Serum level of total bilirubin was significantly higher in the A group than in the non-A group. Serum titers of HBV-DNA and HBe antigen were also significantly higher in the A group, and these may be related to the production of certain types of HBe antigen in genotype A HBV while the other genotypes produce only a single variant of the antigen. Although patients in the non-A group did not develop to chronic hepatitis, 3 of 11 patients in the A group progressed to chronic hepatitis, suggesting that serum HBe antigen promotes immunologic tolerance to persistent viral infection.