Current methods of immunosuppression for heart transplant recipients carry prohibitive risks of infection and bone marrow suppression. Protocols designed to effect specific immunosuppression against the graft without the need for post-transplantation recipient treatment with general immunosuppressants have been tested in rat allograft and hyperacute rejection models and in a xenograft model. Significant prolongation of graft survival has been attained with donor pretreatment methods utilizing in vitro perfusion preservation, cytoxan, ALG and x-irridiation and with recipient pretreatment methods utilizing palladium-109-hematoporphyrin and ALG. These studies will be continued to define an optimal donor-recipient pretreatment protocol in xenograft and allograft models aiming for permanent graft acceptance. In addition, studies are planned to investigate the efficacy of membrane active anesthetic agents and monoclonal specific antimacrophage antisera for use as donor pretreatment agents in a previously developed in vitro preservation system.