We transplanted 46 patients with severe aplastic anaemia with a new pretransplant immunosuppressive regimen consisting of cyclophosphamide (200 mg/kg) and low-dose total body irradiation (3 Gy). This regimen (CY-TBI-2) was designed to decrease the high risk of graft rejection associated with the use of cyclophosphamide alone, without increasing the incidence of graft-versus-host disease (GHVD) or interstitial pneumonia (IPn). Two-year actuarial disease-free survival of patients conditioned with CY-TBI-2 was 62% (95% CI: 47-77%). Only one patient rejected her graft and the incidence and severity of GVHD and IPn were not increased compared to previous studies. Patients less than 25 years of age had excellent 2-year survival of 82% (95% CI: 69-95%). These data indicate that CY-TBI-2 is an effective means of preventing graft-rejection and achieving long-term disease-free survival in multiply transfused patients with severe aplastic anaemia.