Around 5-10% of adults infected with hepatitis B virus (HBV) develop a chronic liver disease such as chronic active hepatitis (CAH), and it is unclear whether the clinical outcome depends solely on the immune response or whether viral factors also play a role. In this study, a search was therefore made for nucleotide mutations in the basic core promoter (BCP) and amino-acid substitutions in the precore/core region of HBV infecting patients with CAH or with acute hepatitis. The nucleotide sequences of the BCP and of the precore/core region were determined in virus from ten patients with CAH and ten with acute hepatitis. The precore/core sequences were also analysed in 14 additional patients (6 with CAH, 8 with acute hepatitis). In seven of the ten patients with CAH, five types of mutations were found in the BCP. Deletions in the precore/core region were observed in six patients. In all six patients where only the precore/core region was studied, amino-acid substitutions were present. In contrast, in the ten patients with acute hepatitis studied for BCP, a mutation was found in the BCP of one patient only. Of the 18 patients in whom the precore/core was studied, three had an amino-acid substitution in this region. The results show a clear link between CAH and both HBV BCP and precore/core region mutations, suggesting these mutations may play a role in the persistence of HBV infection.