Despite remarkable progress in the field of allogeneic organ transplantation, the success of such procedures still depends upon lifelong treatment of the recipient with immunosuppressive drugs. Induction of specific tolerance, which would avoid the need for such drugs, is relatively easy to achieve in rodents by a variety of means including injection of donor blood cells, treatment with anti-donor antibodies [1-5], injection of cells transfected with allogeneic MHC genes [6], and injection of allogeneic MHC class II derived peptides [7]. Use of immunosuppressive drugs such as cyclosporin A has also proven efficient in rodents [8]. However, none of these treatments has led to prolonged unresponsiveness to donor-type MHC antigens in large animal models, including man. Induction of lymphohematopoietic chimerism, through allogeneic bone marrow transplantation (BMT), remains to date the most effective approach to establishing full tolerance to donor type antigens in both small and large animals [9, 10]. However, in spite of encouraging data this protocol is difficult to accomplish in man because of the presence of alloreactive T cells in the bone marrow inoculum, leading to graft-versus-host reactivity. Removal of these T cells from the bone marrow cell preparation also leads to failure of engraftment [11-13]. This review describes an alternative strategy to allogeneic BMT that proposes to induce a" molecular chimerism of MHC antigens" in autologous bone marrow cells. The develop-