The major limitation of mismatched bone marrow transplantation is fatal graft versus host disease (GVHD). We processed haplotype-identical parental marrow with soybean agglutinin (SBA), sheep erythrocytes (SRBC), and neuraminidase-treated SRBC (N-SRBC) to enrich for marrow stem cells and remove mature T cells. Nine patients with severe combined immunodeficiency disease (SCID) who lacked histocompatible donors received these SBA-negative, SRBC-negative, N-SRBC-negative marrow transplants (0.5-5.0 X 10(8) cells/kg). Seven of the nine patients (78%) had documented T-lymphocyte engraftment based on HLA typing and/or chromosomal analysis. Six patients showed evidence of B-cell immunity on the basis of increased immunoglobulin levels, isohemagglutinins, and/or HLA-DR typing of non-T cells. Three patients received marrow ablative chemotherapy pretransplant for maternal-fetal GVHD; neutrophil engraftment occurred between 9 and 17 days posttransplantation, erythrocytes engrafted within 3-4 weeks of transplantation, and platelet recovery was seen between day 17 and day 49 following the transplants. No immunosuppression was given prophylactically posttransplant. Three patients had no GVHD, two had transient rash and/or fever, and two developed mild focal (stage I) chronic cutaneous GVHD. Of the seven who engrafted, five (71%) are alive and clinically well without GVHD 18-35 months posttransplant. These data demonstrate that SBA- and SRBC/N-SRBC-treated haploidentical marrow transplantation results in functional lymphocyte engraftment in SCID without significant GVHD, and can be used for some patients who otherwise would have no hope for survival.