The human C3b receptor (CR1) is a polymorphic glycoprotein comprised of a single polypeptide chain. Of the 4 allotype forms of CR1 that have been described, the 2 most common have Mr's of 250,000 and 260,000, and are regulated by alleles having frequencies in a Caucasian population of 81.5% and 18.5%, respectively. CR1 is present on erythrocytes, neutrophils, eosinophils, monocytes, macrophages, B lymphocytes, some T lymphocytes, mast cells, and glomerular podocytes. CR1 number on erythrocytes is genetically regulated, and ranges from less than 100 sites per cell to greater than 1000 sites per cell, the average in the normal population being 500-600 sites per cell. A model accounting for this wide distribution proposes the existence of 2 codominant alleles determining low and high receptor number respectively; CR1 number is not affected by the structural polymorphism, so that the loci for these two phenotypic characteristics are distinct. The function of CR1 on erythrocytes may be to promote the clearance of immune complexes from the circulation. CR1 number on myelomonocytic cells is regulated by chemotactic factors which can rapidly transfer CR1 sites from a latent, presumably intracellular, site to the plasma membrane of these cells, thereby enhancing their ability to interact with opsonized foreign material. The receptor is involved in the endocytic reactions of these cells, and recent findings have demonstrated that this function can be modulated by T cell-derived factors, fibronectin, and phorbol esters. The role of CR1 on lymphocytes remains to be fully explored, although the receptor may enhance the differentiation of B cells into antibody-secreting cells.