HEMATOPOIESIS IS A complex process in which pluripo-tent stem cells proliferate and differentiate to generate the full complement of mature blood cells. More than 30 hemopoietic cytokines and growth factors that increase or decrease progenitor proliferation and differentiation have been cloned and characterized. 1-3 Although the biological effects of these cytokines and growth factors on stem and progenitor cells has been extensively studied, we still do not understand how this extremely orderly hematopoietic process is regulated. Under steady-state conditions, hematopoiesis takes place within the bone marrow microenvironment. Stem cells and their progeny interact relatively specifically with cell and extracellular matrix (ECM) ligands present in the marrow but not other microenvironments. 4-6 These adhesive interactions are responsible for the retention of hematopoietic cells in the marrow. Like hematopoietic cells, hematopoietic cytokines and growth factors bind to some specific extracellular matrix components7, 8 and stromal cells can express certain cytokines on their surface. 9 Selective adhesion of progenitors and cytokines to ECM components or stromal cells then results in the colocalization of progenitors at a specific stage of differentiation with a specific array of cytokines, in so-termed niches. 10, 11 This provides one level of growth and differentiation regulation. There is also mounting evidence that contact interactions per se between progenitors and marrow stromal ligands play an important role in the regulation of the hematopoietic process. 12-14 Adhesive interactions themselves may serve as growth or survival signals or adhesion itself may modulate cytokine-or growth factordependent signals. These contact-mediated cues may be responsible for regulating the orderly progression of hematopoiesis. More than 20 different adhesion receptors have been identified on hematopoietic progenitors. 15, 16 These include members of the integrin family responsible for adhesion to ECM components (fibronectin, collagen, laminin, or thrombospondin) 17 or cell surface-expressed cell adhesion molecules (CAM; vascular [VCAM] and intracellular [ICAM]). 18, 19 Progenitors express CD44, 20 which supports adhesion to hyaluronate20, 21 and fibronectin. 22 Platelet-endothelial-(PE) CAM-1, a member of the Ig superfamily of cell adhesion molecules, and L-selectin are expressed on progenitors. 23, 24 Finally, several sialomucins have been found on progenitors, including the stem cell antigen, CD34, 25 CD43, 26, 27 CD45RA, 28 P-selectin glycoprotein ligand-1 (PSGL-1), 29 and CD164, described by Zanettino et al30 in this issue of BLOOD. 31 Other members from this family not expressed on hematopoietic cells include glycosylationdependent cell-adhesion molecule-1 (Glycam-1) 32 and mucosal addressin cell adhesion molecule-1 (Madcam-1). 33 Which of these receptors is responsible for the specific retention of stem and progenitor cells in the marrow microenvironment or the homing of progenitors to the marrow is not known. In vitro, adhesion of CD34+ cells to stromal feeders can be blocked by antibodies against the majority of these receptors. 17-24, 30, 31 In vivo experiments have suggested a relatively predominant role of ß1-integrins in the retention of progenitors in the marrow and progenitor homing to the marrow. 34-36 However, ß1-integrins and their ligands are ubiquitously expressed and ß1-integrins cannot provide for the rather exclusive progenitor-marrow interactions. Thus, another receptor (s) must be responsible for the specific stem cell-marrow interactions. The mucin receptor, CD164, described by Zanettino et al, 30 or similar …