It has been shown previously that sera from patients with cholestatic liver diseases react with sulphite oxidase (SO) prepared from chicken liver. In order to analyse this reactivity and the clinical relevance of anti-SO antibodies in more detail, we produced human recombinant SO. Human recombinant SO (60 kDa) was expressed in Escherichia coli and applied to enzyme-linked immunosorbent assay and Western blot. Sera from patients with autoimmune liver disorders [primary biliary cirrhosis (PBC) n = 96; autoimmune hepatitis (AIH) n = 77; primary sclerosing cholangitis (PSC) n = 39], and from patients with other hepatic (n = 154) and non-hepatic chronic inflammatory disorders (n = 113) were investigated. Highest incidence and activities of IgG-anti-SO antibodies were observed in PSC patients. Nine of 16 untreated (56%) and four of 23 PSC patients treated with ursodeoxycholic acid (UDCA) (17%) were positive. Antibody activity decreased significantly during UDCA treatment. Five per cent of PBC and 9% of AIH patients, but also 15% of patients with alcoholic liver disease, were IgG anti-SO-positive. In patients with viral hepatitis and non-hepatic disorders they could be hardly detected. Anti-SO antibodies are further anti-mitochondrial antibodies in chronic liver diseases. They occur predominantly in PSC, and UDCA treatment seams to decrease antibody activity. Whether these antibodies are primary or secondary phenomena and whether they are related to the aetiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.