In this study, a previously not documented variant of hepatitis B virus was described in Chinese patients with fulminant hepatitis. The entire precore/core region amplified from samples was cloned into a bacterial vector and sequenced by dideoxy chain termination reaction. Double amino acid substitutions were seen in the precore region in the isolates: one from glycine to aspartic acid at codon 29 previously reported; the other substitution of phenylalanine for valine at codon 17 in the cleavage site of hepatitis B virus. Loss of hepatitis B virus e antigen in these patients with fulminant hepatitis might therefore be due to the mutation in the cleavage site, rather than the emergence of a stop codon in the precore region of hepatitis B virus. Accumulation of hepatitis B e antigen precursor within the hepatocytes might account for the fulminant hepatitis exacerbation.