An autosomal recessive type of severe combined immunodeficiency disease (SCID) was characterized by an absence of immunoglobulins (Ig) in the serum and of Ig+ lymphocytes in bone barrow (BM) and peripheral blood. In the BM CD10+/terminal deoxynucleotidyl transferase-positive lymphocytes were identified. Epstein-Barr virus-transformed B lymphoblastoid cell lines (BLCL) obtained from BM and peripheral blood did not synthesize Ig. The Ig heavy and light chain gene complexes in the BLCL had retained the germ-line configuration. Mature T cells were present but their numbers in peripheral blood were decreased. T lymphoblastoid cells derived from peripheral blood expressed normal T cell receptor (TcR) CD3 complexes and manifested various genomic TcR rearrangements. It was concluded that this type of SCID entailed a complete arrest of B lymphocyte differentiation in an early stage prior to Ig rearrangements and a quantitative defect of T lymphocytes which nevertheless allowed development of mature T cells. Repeated failures of BM transplantation and the striking absence of Ig assembly suggested that this SCID defect resides in the BM microenvironment.