This study describes a mUrine model of autoimmune hepatitis: experimental autoimmune hepatitis. Experimental autoimmune hepatitis could be induced most effectively in male C57BL16 mice by intraperitoneal immunization with the 100, OOO gsupernatant of syngeneic liver homogenate (S-100) in complete Freund's adjuvant. BALB/C and C3H mice were less susceptible than C57BL/6 mice. Experimental autoimmune hepatitis could not be induced in Lewis rats. Intraperitoneal immunization was more effective than intramuscular or subcutaneous injections, and the amount of protein administered above a threshold was of little influence. A single intraperitoneal injection of 5-100 in complete Freund's adjuvant resulted in hepatitis of at least 6 mo duration. Histological changes were most marked 4 wk after disease induction. The histological findings were characterized mainly by perivascular inflammatory infiltrates and hepatocyte necroses. The histological changes were accompanied by biochemical evidence of liver cell death. Passive transfer of experimental autoimmune hepatitis with concanavalin A-activated splenocytes was possible. Specific T-cell reactivity against fractions of S-100 could be demonstrated in vitra Thus experimental autoimmune hepatitis is a murine model of autoimmune hepatitis probably mediated by autoreactive T cells. It will allow studies of the pathogenesis of autoimmune hepatitis. (HEPATOLOGY 1990,11:24-30.) Autoimmunity has been recognized as the underlying mechanism in different subgroups of chronic active hepatitis. Characteristic autoantibodies and the response to immunosuppressive therapy have provided evidence for an autoimmune origin (1, 2). The study of autoimmune hepatitis has been hampered by the lack of adequate and reproducible animal models. In recent