A 2 1/2-year-old male infant with severe combined immunodeficiency was documented by HLA typing and the presence of a female karyotype in the few spontaneously dividing cells to have an intrauterine-derived maternal lymphocyte graft. The presence of DR antigens on the engrafted maternal E rosette-forming T cells was demonstrated by both cytotoxicity and immunofluorescence techniques using both conventional and monoclonal antihuman DR antisera. These DR antigens were of the same allospecificity, DR4, as the mother's peripheral blood B cells. The patient's B cells and monocytes expressed DR alloantigens DR4 and DR3, corresponding to his genotype. Although fresh maternal lymphocytes react strongly in vitro against patient non-T cells, the engrafted maternal T lymphocytes no longer show this activity. Furthermore, clinical evidence suggesting mild graft-versus-host disease was completely resolved by the end of his first year. The presence of the DR-positive maternal cells may reflect the survival of a group of activated suppressor cells mediating graft tolerance of host tissue.