[Background] When orthotopic liver transplantation from Wistar Furth(WF) rats to Lewis(LEW) rats, the grafts were rejected within 38 days (n=8; mean graft survival 26.3±8.3 days). In the present study, effect of anti-CD4 monoclonal antibody(OX-38) on graft survival was investigated. [Methods] Five recipient rats were treated with OX-38 on day 0 and 2 after transplantation, respectively, and OX-38 was not given in eight recipient rats. In treated rats survived longer, immunological responses were examined using MLR and CTL assay.[Results] The grafts in 4 of the 5 rats received OX-38 survived for 65, >80, >90 and >200 days, respectively. While levels of serum bilirubin elevated more than 10 mg/dl in 2 weeks postoperatively in untreated rats, the levels were below 5 mg/dl and return to normal range within 8 weeks in treated rats. We investigated immunological responses in long-survived LEW rats recieved with antibody therapy after transplantation. Proliferative response was observed in spleen cells from LEW rats with WF liver transplants in vitro stimulation with LEW spleen cells. Furthermore, in the MRL culture, cytotoxicity against WF Con A blast was generated. [Conclusions] OX-38 has preventive effect on rejection of transplanted liver from WF to LEW rats. From immunological studies, cellular responses against donor antigen were observed in long-term survived rats. On the other hand, anti-CD8 mAb shows no preventive effect on liver graft in this system.