Human sera were examined by immunoblotting for antibodies against the polymerase (reverse transcriptase) believed to be encoded in the P open reading frame (ORF) of human hepatitis B virus (HBV). Sera from patients with self-limited and chronic hepatitis reacted specifically with fusion proteins containing different domains of the P ORF. The results indicate that this ORF is expressed, and that the corresponding proteins contain at least two immunogenic domains. In contrast to human immunodeficiency virus, induction of antibodies against reverse transcriptase appears to be less common for HBV, and may depend on long persistence of infection.