We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.