The pathogenesis of fulminant hepatitis B virus (HBV) infection is not well understood. The aim of this study was to investigate whether there is an association between specific viral variants and a fulminant disease course. The entire HBV genomes from the serum of eight patients with fulminant HBV infection and one patient with fulminant hepatitis during reinfection after liver transplantation were investigated. After isolation and amplification of viral DNA by polymerase chain reaction (PCR), plus and minus strands were directly sequenced. Sequence data were analyzed by comparative sequence alignments with 35 and 2 complete HBV genome sequences from patients without and with fulminant hepatitis, respectively. Several point mutations were present in all regions of the genomes. Many nucleotide changes had never or rarely been found in the reported HBV isolates from patients without fulminant hepatitis. A distinct mutation present in all genomes was not identified. Clusters of rare and unique mutations were observed in the enhancer II core promoter region. Mutations previously suggested to be associated with fulminant HBV infection were not consistently found. A precore stop codon mutation at nucleotide position 1896 or an A-to-T mutation at nucleotide position 1762 and a G-to-A mutation at nucleotide position 1764 in the core promoter region were present in four and three cases, respectively. Fulminant HBV infection does not appear to be caused by a specific genomic mutation. However, various mutations clustering in the enhancer II core promoter region may contribute to a fulminant disease course.