1. Previous studies have demonstrated the presence of antibodies to trifluoroacetylated hepatic proteins (TFA-proteins) in sera from patients with the severe form of halothane-associated hepatitis (halothane hepatitis). The TFA-proteins are produced via cytochrome P450-mediated metabolism of halothane to the reactive species TFA-chloride. 2. To investigate the presence of autoantibodies (which recognize various non-TFA-modified human hepatic polypeptides) in patients with halothane hepatitis immunoblotting experiments were performed using microsomal fractions prepared freshly from livers of five different (halothane-free) tissue donors. Blots were developed using 15 well-characterised sera from patients with halothane hepatitis. 3. Autoantibodies to human hepatic polypeptides were detected in most, but not all, of the patients' sera. The pattern of antibody reactivity varied markedly between sera. Although no common pattern of antibody recognition was observed, polypeptides of molecular mass between 60 and 80 kDa were the predominant targets. A similar protein recognition pattern was seen when each positive serum was tested against the five individual human liver samples. 4. Such autoantibodies were not detected in sera from 16 normal human blood donors, but were detected in three of six sera from patients exposed to halothane without developing hepatitis. 5. The autoantibodies are thought to arise in patients exposed to halothane as a consequence of a halothane-induced immune response to chemically-modified proteins. Such antibodies could contribute to the complex pathological processes involved in halothane hepatitis.