Mouse hematopoietic stem cells can be enriched from adult bone marrow by a number of methods. The resulting cell populations are heterogeneous in function, suggesting a complex organizational structure within the stem cell compartment. Several assays can be applied to the study of early stages of hematopoiesis; however clonal assays for long-term repopulation, the most critical operational definition of hematopoietic stem cells, are lacking. Further complicating the prospect of understanding early hematopoiesis is the finding that genetic variations among laboratory strains of mice lead to major differences in phenotypic and functional characteristics of hematopoietic stem cells. Application to the human situation of the methodology developed for stem cell isolation and characterization in the mouse will be hampered by the possibility of genetic variations among human subjects and the lack of a well-characterized assay system to detect and quantify cells capable of long-term repopulation of irradiated recipients.