The syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3⁺ lymphocytes and 50% of his CD19⁺ lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3⁺CD4^-CD8^- with T-cell receptor γδ heterodimers and CD3⁺CD4^-CD8⁺ with CD8αα homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs. (Blood. 2004;103:1171-1174)