A system in which immune-deficient mice are repopulated with cells from the human myeloid lineage, and that provides an in vivo stem cell assay for human hematopoietic cells is described. Generation of the chimeric human/immune-deficient (HID) mice was dependent on the use of immune-deficient bg/nu/xid mice. Infusion of these mice with human bone marrow gave rise to increases in human macrophage progenitors during more than 5 weeks of in vivo growth, indicating the seeding, proliferation, and differentiation of human stem cells. The human identity of the progenitors was confirmed by sequence analysis and their dependence on human growth factors. The creation of HID mice lays the foundation for establishing animal models for a wide variety of human hemopathies, from leukemia to infectious disease.