Bone marrow transplantation has resulted in life-saving sustained T-cell reconstitution in many infants with severe combined immunodeficiency (SCID), but correction of B-cell function has been more problematic. At the annual meeting of the Primary Immunodeficiency Treatment Consortium held in Boston, Massachusetts, on April 27, 2012, a debate was held regarding the use of pretransplantation conditioning versus no pretransplantation conditioning in an effort to address this problem. Reviews of the literature were made by both debaters, and there was agreement that there was a higher rate of B-cell chimerism and a lower number of patients who required ongoing immunoglobulin replacement therapy in centers that used pretransplantation conditioning. However, there were still patients who required immunoglobulin replacement in those centers, and therefore pretransplantation conditioning did not guarantee development of B-cell function. Dr Rebecca H. Buckley presented data on B-cell function according to the molecular defect of the patient, and showed that patients with IL-7 receptor ⍺, ADA, and CD3 chain gene mutations can have normal B-cell function after transplantation with only host B cells. Dr Elie Haddad presented a statistical analysis of B-cell function in published reports and showed that only a conditioning regimen that contained busulfan was significantly associated with better B-cell function after transplantation. The question is whether the risk of immediate and long-term toxicity with use of busulfan is justified, particularly in patients with SCID with DNA repair defects and in very young newborns with SCID who will be detected by using newborn screening.