The cytokine receptor common gamma chain mutation in X-linked SCID results in a failure of T and NK cell development and an as yet undefined defect of B cells. Using immunoglobulin isotype-specific reverse transcription-PCR we show that although hematopoietic stem cell transplantation restores a diverse repertoire of class-switched B cell clones, on further analysis these are almost all of donor origin. This suggests that host B cells, which predominate after unconditioned transplantation, are still defective even in the presence of normal T cells. These studies imply that effective humoral reconstitution can only be achieved by the engraftment of normal donor B cells.