A CELL ADHESION molecule (CAM) has been defined as a cell surface receptor capable of attaching a cell either to another cell or to an extracellular matrix (ECM) substrate through interaction with its ligand. CAMs are often thought of as the glue holding cells to each other or to a matrix. Indeed, CAMs may simply integrate structural, intracellular proteins with substrate. Cell adhesive interactions also may result in the transmission of chemical and mechanical signals across membranes, thus providing important cues regulating many aspects of a cell's behavior such as proliferation, differentiation, and migration. The affinity of individual cell adhesion interactions is usually low (KD ranges from 10 -8 to 10 -5 mol/L), but because CAMs typically adhere by multiple attachments, high-avidity interactions result from individually weak ones. 1 This definition of CAMs excludes interactions between cell surface receptors and soluble molecules (cytokines and small peptides), although this distinction may be somewhat blurred. For example, the interaction between the membrane-bound form of the cytokine, steel factor, found on bone marrow stromal cells and its receptor, c-kit (CDI17), on hemopoietic progenitors, can lead to sequestration of stem cells in particular microenvironments, and in this context functions as an adhesion receptor of stromal cells. This is in addition to steel factor's well-defined function as a cytokine, which is essential for the progenitor cell's survival and proliferation. 2 In recent years, a large number of CAMs have been characterized, and their expression and function on cells of various lineages has been explored. The plethora of CAMs may be grouped into a number of superfamilies, based on their related primary structures. The different superfamilies mediate different types of functions, ranging from very stable interactions, through promigratory interactions that allow cells to move, to very transient interactions that serve to arrest cell movement (reviewed in references 1, 3, 4). Erythroid precursors express a number of CAMs, several of which have a functional role in erythroid differentiation. 5 From studies of blood group active membrane proteins, it is now clear that mature red blood cells (RBCs) also express a number of glycoproteins (gps) that either are known to function as CAMs [the LW, Lutheran (Lu) and Indian (CD44) gps] or by virtue of their close structural homology with known CAMs are thought to have similar function (the Ok a and Xg a gps). 6 Mature RBCs also express the non-blood group-active CAMs CD47 (Rh-associated gp, IAP), CD36 (thrombospondin receptor), and CD99 (Xga-associ ated sialomucin). This review describes the structure, tissue distribution, and ligand-binding properties of the different CAMs that are expressed on erythroid cells, and their function in erythropoiesis is discussed. We will discuss CAM deficiencies found in blood group null phenotypes and focus on the contribution of erythroid CAMs to the pathology of disease states.