Our knowledge of the organization and regulation of the murine hematopoietic stem cell hierarchy has, in large measure, been the result of the development of in vivo reconstitution assays for cells of various levels of differentiation. For example, many basic stem cell concepts were established using CFU-S as a paradigm. Although there are no clonal assays for the earliest pluripotential cells, they can nevertheless be quantitated based on their ability to reconstitute animals with a deficient hematopoietic system. A similar understanding of the human hematopoietic system has lagged because of the lack of a suitable assay for human stem cells. Using several different approaches it has become possible to transplant human hematopoietic cells into immune-deficient mice. Since both lymphoid and myeloid cells have been engrafted, these experiments may lay the foundation for an assay for human pluripotent stem cells. Moreover it should now become possible to establish experimental animal models of a large number of human hemopathies including leukemia.