Mitogenesis, cellular aggregation, and motility follow upon the interaction of fibrinogen with certain defined cell surface receptors. In addition to circulating platelets and vascular endothelium, monocytes express what appears to be a receptor for fibrinogen. Evidence is presented here that the leukocyte adhesion receptor Mac-1 can be specifically induced to bind fibrinogen with characteristics immunochemically and functionally distinct from the established Arg-Gly-Aspdirected fibrinogen receptors. The competence of Mac-1 as a fibrinogen receptor is a general property of cells of monocyte and myeloid lineage acquired after maturational changes of some regions of the~ t subunit of Mac-1 during the process of cell differentiation. This ligand recognition specificity of Mac-1 is lacking for the resting cell. Rather, induction of fibrinogen binding capacity of Mac-1 is due to a cellular response to selected agonists characterized by inducing rapid transients of cytosolic Ca 2÷. Although different in activation pathways and recognition specificity, Mac-1 exhibits an oligospecific ligand versatility characteristic of other homologous Arg-Gly-Asp-directed adhesion receptors. variety of highly specific interactions between cells, as well as between cells and extracellular matrix, guide and orientate a variety of important biological responses. Disparate processes including embryonic development (37), organ function (20), and immune and inflammatory mechanisms (32) are representative of fundamental cellular processes requiring participation of general adhesion mechanisms. A family of highly differentiated receptors modulate processes of cell-cell communication as well as cellular interaction with extracellular matrix. These receptors designated" integrins" are members of a superfamily of homologous molecules one or more of which are synthesized and expressed by most if not all diploid cells (14). These are heterodimeric, transmembrane glycoproteins (GPs)~, composed of noncovalently linked a and 13 subunits and some functionally recognize the Arg-Gly-Asp (RGD) sequence in the context of contiguous residues as a ligand sequence (28). Common characteristics of the integrin family are their functional versatility and ligand multispecificity (29). High affinity saturable binding of a select few ligands, ie, oligospecificity, is exemplified by the platelet adhesion receptor GPIIb/IIIa which binds three different and nonhomologous adhesive proteins, ie, fibrinogen, fibronectin and von Wil-