Hematopoietic microenvironment is comprised of an admixture of several adherent cell types including fibroblasts, reticular adventitial cells, and marcophages. The biologic interaction of these cells with the most primitive hematopoietic progenitor cells capable of reconstituting all hematopoietic lineages within an irradiated host, as well as differentiated progenitor cells and cells of each committed lineage, has been the subject of intense investigation. Transplantation of the hematopoietic microenvironment has recently been demonstrated and this technique has been used to partially correct the microenvironmental defect in the Sl/Sld mouse. The molecular mechanism of cell surface interaction between stromal and hematopoietic stem cells is being elucidated by molecular transfection techniques in which genes for specific receptors are introduced into hematopoietic stem cell lines and then demonstrated to adhere and proliferate in contact with stromal cells expressing transfected recombinant ligands. This model has been demonstrated with the EGF receptor bearing 32D cl 3 stem cells bound to TGF alpha-producing stromal cells. Extracellular matrix components of the adherent cell layer, the binding of hematopoietic growth factor interaction with matrix components, as well as the positive and negative feedback regulatory role of hematopoietic stem cells bound to the microenvironment, represents the focus of current investigation.