A process unique to lymphocyte differentiation is the rearrangement of genes encoding antigen-specific receptors on B and T cells. A mouse mutant (CB-17scitf) with severe combined immune deficiency, ie, that lacks functional B and T ceils, shows no evidence of such gene rearrangements. However, rearrangements were detected in Abelson murine leukemia virus-transformed bone marrow ceils and in spontaneous thymic iymphomas from CB-17scid mice. Most of these rearrangements were abnormal:-80% of Igh rearrangements deleted the entire Jh region, and~ 60% of TCR6 rearrangements deleted the entire Jp2 region. The deletions appeared to result from faulty D-to-J recombination. No such abnormal rearrangements were detected in transformed tissues from control mice. The scid mutation may adversely affect the recombinase system catalyzing the assembly of antigen receptor genes in developing B and T lymphocytes.