A model system in AKR mice for the induction and cure of a clinically evident graft-versus-host disease is reported. Graft-versus-host disease is inititated by i.p. injections of ecyclophosphamide (250 mg/kg body weitht ) into female AKR mice, on Day 0. This is followed by i.v. injections of 45 x 10-6 normal spleen cells (NSC) from male C57BL/6J mice. Median survival time for these mice is 33.4 plus or minus 4.5 days. Following the administration of C57BL/6J NSC, AKR mice were rescued from graft-versus-host disease by the following treatment protocol: (a) Day 6, 35 x 10-6 DBA/2 NSC given i.v.; (b) Day 10, cyclophosphamide i.p. (150 mg/kg body weight); (c) Days 11 and 26, 35 x 10-6 AKR NSC given i.v. These experiments demonstrate that graft-versus-host reaction can be elminiated by coupling a graft-versus-host reaction with a graft-versus-graft reaction and restoring the host by immunocompetent syngeneic cells.