Human severe combined immunodeficiency (SCID) includes an X-linked SCID (XSCID) characterized by a complete absence of mature T cells, hypogammaglobulinemia and a normal or elevated number of B cells. XSCID results from mutation in the IL-2 receptor (IL-2R) gamma chain gene, which is thought to be involved in not only IL-2R but also IL-4R and IL-7R mediated signals. To investigate the VDJ recombination and Ig repertoire development in the absence of the IL-2R gamma chain, we intended to study the CDR3 junction in peripheral blood B cells of three XSCID patients. A total of 101 different CDR3 junctions were cloned following polymerase chain reaction amplification of polyclonal peripheral blood lymphocyte DNA. Sequence analysis of CDR3 junctions revealed that the primary antibody repertoire of the Ig H chain gene was assembled in a normal fashion. Among the JH segments, overexpression of JH3 segments was significant in XSCID patients compared with age-matched controls. D segment usage in XSCID was very similar to that in age-matched controls. All of the XSCID JH regions except for two clones were equal to germline JH genes, showing little or no evidence of somatic mutation. The results indicate that the immature JH segment is preferentially utilized and somatic mutation is absent in the CDR3 junction of the Ig H chain gene of XSCID patients.