The role of Class I major histocompatibility (MHC) antigens in the induction of specific suppression of graft rejection has been investigated. Two experimental transplantation models have been used ’ fully vascularized heterotopic Cardiac altografts in the mouse and fully vascularized orthotopic renal allografts in the rat. Preparations of ceils expressing Class I MHC antigens, for example highly purified preparations of rat erythrocytes or platelets or mouse L cells (H2k) transfected with the D locus Class I gene of the b haplotype, LDb-1 cells, were used to pretreat recipients prior to transplantation, The function of the allograft was monitored in order to assess any beneficial effects induced by Class I MHC antigens. The results obtained implicate Class I MHC as important in the induction of specific immunosuppression of vascularized allograft rejection.