For the induction of experimental chronic active hepatitis (CAH) in rabbits long term immunization was performed with human liver-specific protein plus complete Freunds adjuvants. Serum antibodies against allogeneic hepatocellular membrane antigens could be detected after 23 weeks using isolated normal rabbit hepatocytes or by the passive hemagglutination technique with liver-specific membrane protein as antigen. Isolated hepatocytes from these rabbits showed in vivo fixed IgG on their plasma membranes in a linear and granular fluorescence pattern. Furthermore immune complexes (Raji-cell test) were detectable in the sera of these animals. After 23 weeks 3 out of 16 animals had developed a chronic active hepatitis (CAH). After 44 weeks 10 of 15 animals and after 78 weeks 6 of 7 surviving animals had a CAH. All these 7 animals had serum antibodies against membrane antigens of isolated rabbit hepatocytes and in vivo fixed IgG on their hepatocellular plasma membranes. The results suggest the existence of autoantibodies against hepatocellular membrane antigens. In addition, immune complexes may be bound to the plasma membranes. The pathogenetic role of these humoral immune reactions has yet to be determined.