Ah interferons display antiviral properties, but gamma-interferon especially has an immunomodulatory effect and may induce autoimmune phenomena. Therefore the formation of autoantibodies was investigated in patients with chronic hepatitis B treated with gamma-interferon. Eleven patients (all HBs-Ag and HBe-Ag positive) were treated for 6 months with recombinant gamma-interferon. The following antibodies were tested: anti-nuclear antibodies, smooth muscle antibodies, anti-actin, anti-mitochondrial antibodies of subgroup anti-M2 and anti-M9 as well as naturally occurring antibodies, antibodies to liver-kidney microsomes, vascular endothelial cell antibodies, sarcolemmal antibodies, parietal cell antibodies, thyroglobulin antibodies and antibodies to laminin and keratin. All patients produced autoantibodies during therapy. The maximum antibody formation and the highest titres were observed in the period between the 3rd and 6th month after therapy began. The cumulative frequencies of the different antibody specificities were as follows: n=6 anti-nuclear antibodies, n=7 smooth muscle antibodies, n=1 anti-actin, n=12 antibodies to laminin or keratin, n=6 endothelial cell antibodies/sarcolemmal antibodies, n=6 anti-mitochondrial. antibodies, n=1 antibodies to liver-kidney microsomes, n=2 thyroglobulin antibodies, n=4 parietal cell antibodies. Antibodies persisted in six patients over a period of 3 months (two cases of parietal cell antibodies and one case of antibodies to liver-kidney microsomes) and were still detectable in three patients 6 months after therapy. In three patients new antibody formation occurred 1 month after therapy. So far, clinical signs of an autoimmune disorder have not appeared in any of the patients. In conclusion, a high frequency of antibodies was induced by gamma-interferon therapy. The persistence of organ-specific antibodies indicates autoimmunity, which needs careful observation in further follow-up. (C) Journal of Hepatology.