Personal experience is outlined with a preparative regimen consisting of total nodal irradiation (TNI) and cyclophosphamide in patients with severe aplastic anemia undergoing bone marrow transplantation (BMT). Nine patients (median age 23) previously having blood transfusions received BMT at the BMT Center in Pesaro. All patients were prepared for transplantation with cyclophosphamide 50 mg/kg/day (day -6, -5, -4, -3), and 7.5 Gy total nodal irradiation day -1, with a dose rate of 26 cGy/m. Six out of eight evaluable transplanted patients are still surviving 3 to 23 months with a median follow-up of 16.5 months. This preoperative regimen is extremely effective in decreasing rejection following transplantation for severe aplastic anemia. Future investigation must be aimed at the elimination of graft-versus-host-disease and control of fatal infections.