Levels of anti-albumin autoantibodies (AAA) of the IgG class were determined by ELISA in sera of patients with acute and chronic hepatitis B virus (HBV) infection. Mean AAA levels were higher than normal in both acute and chronic hepatitis patients. AAA levels were higher than the upper normal limits in practically all patients with acute self-resolving hepatitis, and decreased to normal levels when the patients recovered. Enhanced IgG AAA levels were observed in many patients with chronic hepatitis and serological markers of HBV replication. Elevated AAA levels were not associated with either more elevated transaminase levels or more severe histological forms of chronic hepatitis. The results of this study suggest that the interaction of albumin with HBV determinants is involved in AAA elevations, probably by mediating an increase in albumin immunogenicity. Moreover, the fall in AAA levels in the recovery phase of acute hepatitis, the coexistence of elevated levels with HBeAg and HBV-DNA, and the lack of correlation between AAA levels and different evolutive forms of chronic hepatitis, seem to exclude AAA from playing a relevant role, be it protective or damaging, during HBV infection.