Widespread clinical application of cardiac transplantation for the treatment of end stage cardiac failure awaits progress in dealing with rejection. Methods for decreasing graft antigenicity by modulation of the donor afford the dual benefit of blunting the rejection response and permitting decrease in the levels of toxic but currently requisite immunosuppressive drugs. The proposed study examines, in an inbred rat cardiac transplantation model, the effects of donor treatment with cyclophosphamide, antilymphocyte globulin, radioporphyrins and x-irradiation on prolongation of allograft survival in the unmodified host. Parallel in vitro studies utilizing leukocyte isotope labelling techniques are proposed to test the hypothesis that donor pretreatment effects prolongation of graft survival by depleting graft passenger leukocytes.