We report fatal reticular dysgenesis in a premature infant presenting with severely decreased blood and bone marrow granulocytes and lymphocytes, an absent thymic shadow by x-ray film, and generalized lymphoid hypoplasia. Immunologic and electron microscopic evaluation of his white blood cells demonstrated that, despite extremely low cell numbers, cells from all stages of both granulocytic and lymphocytic development were present. Immature bone marrow cells of both myeloid and lymphoid lineages were found in much greater proportions than were mature cells; preB cells outnumbered B cells by more than tenfold. Megakaryocytes and erythroid cells appeared to be present in normal numbers, and tritiated-thymidine incorporation by bone marrow nucleated cells was also normal, although it may have largely occurred in erythroblasts. These data suggest that the primary defect in reticular dysgenesis is not failure in initiation of stem cell differentiation along lymphoid and myelomonocytic lines but rather an, as yet, undefined abnormality that interferes with normal growth and maturation of immune cells committed to these differentiation pathways. © 1985, American Medical Association. All rights reserved.