A new combination of total lymphoid irradiation and cyclophosphamide was used prior to bone marrow transplantation in an attempt to achieve decreased rejection rates and graft vs. host disease. Nine previously transfused patients with severe aplastic anemia received marrow from an HLA-identical, MLC[mixed lymphocyte culture]-compatible sibling following this preparative regimen. There was no graft rejection, and only 1 patient developed graft vs. host disease. Of the 9 patients, 7 (78%) survived with a median follow-up of 400 days. The excellent results of this pretransplant combination of total lymphoid irradiation and cyclophosphamide warrants application of this regimen to a larger series of patients.