Since the introduction of methods for depleting T lymphocytes from human allogeneic marrow grafts in 1980, such transplants have been increasingly used as a source of lymphoid progenitors for the curative treatment of patients with lethal genetic disorders of immunity who lack an HLA matched sibling donor. This review of the results of HLA-haplotype disparate T-cell depleted marrow grafts applied to the treatment of severe combined immunodeficiency (SCID) indicates that such transplants can lead to durable engraftment and successful reconstitution of immune function without severe graft vs. host disease in a high proportion of cases. Resistance to engraftment and selective abnormalities of B cell development and function in the post transplant period constitute major obstacles to the success of these transplants. However, considerable progress has been made towards the elucidation of the cellular mechanisms responsible for graft resistance, graft-host tolerance and either the full or limited immunologic reconstitutions achieved.