Allogeneic bone marrow transplantation following a lethal dose of cyclophosphamide was studied in 20 donor-recipient pairs of dogs. Eighteen of these were littermate pairs matched with four canine histocompatibility typing sera, and two were pairs of unrelated mismatched dogs. Ten dogs died in the 1st week from infection, bleeding, and nonhemopoietic drug toxicity. Their survival was too short to evaluate the success or failure of the marrow graft. Evidence for allogeneic bone marrow engraftment was demonstrated in 8 of the 10 recipients that lived beyond 7 days. Five of the dogs with marrow engraftment died within 36 days, 1 with evidence of graft-versus-host disease, 1 with pneumonia, and 3 after rejection of the marrow graft. Three of the 8 dogs with marrow grafts became long-term chimeras. Two are alive 350 and 450 days after transplantation. Peripheral blood, bone marrow, and lymph nodes in these 2 dogs showed a mixed population of host and donor cells. One additional dog survived over 8 months with evidence of a persistent change to donor red cell type and with prolonged survival of a skin graft from the marrow donor. In addition, this dog developed an isoantibody against the former host red cell type. It was concluded that persistent hemopoietic chimerism can be obtained in outbred animals following a lethal dose of cyclophosphamide.