Donor-specific unresponsiveness to organ allografts remains an elusive goal in clinical transplantation, as most successful experimental protocols for the production of antigen-specific immunosuppression require lengthy recipient pretreatment. The use of an induction course of antilymphocyte serum (ALS) beginning at the time of transplantation, followed by the transfusion to the recipient of donor-specific bone marrow, has been shown in animals to induce prolonged allograft survival and is applicable for use in cadaver donor clinical transplantation. Our preliminary data in humans suggest that the transfusion of cryopreserved cadaver donor bone marrow following a short course of ALS is safe and does not induce graft-versus-host disease or allograft rejection. Twenty patients have been included in the protocol and 19 have been discharged from the hospital with functioning kidney transplants. One graft failed at 3 months. Eight patients have been withdrawn entirely from prednisone immunosuppression 3-6 months following transplantation. The contralateral kidneys from the marrow donors were transplanted into an additional 20 patients who received sequential immunosuppressive therapy without marrow transfusion. Three of these grafts have failed within 3 months due to acute rejection. Donor marrow transfusion may give rise to improved allograft and patient survival in clinical transplantation while at the same time allow for reduced requirements for nonspecific immunosuppressive agents with their undesirable side effects.