Hematopoietic stem cell chimerism can be established after low-dose conditioning regimens, although the risk of donor cell rejection increases for unrelated donor transplantations. We added pretransplantation rabbit antithymocyte globulin (6 mg/kg) to an established conditioning regimen of fludarabine (90 mg/m2) and single-fraction total body irradiation (200 cGy) followed by postgrafting immunosuppression with cyclosporine A and mycophenolate mofetil for 22 patients with hematologic malignancies. One patient rejected the graft and successfully underwent transplantation with cells from a second donor by using the same conditioning regimen. The actuarial probability of developing acute graft-versus-host disease grade II to IV before day 100 was 40%, although 9 of 14 patients who survived beyond 100 days developed chronic graft-versus-host disease. These data support a hypothesis that the addition of antithymocyte globulin decreases the risk of graft-versus-host and host-versus-graft reactions when combined with a nonmyeloablative conditioning regimen of fludarabine and total body irradiation.