We describe a molecule on the surface of human peripheral blood monocytes that appears to be a plasma membrane receptor for fibronectin. We have identified this protein using a monoclonal antibody, A6F10, which prevents the interaction between monocytes and substrate-bound fibronectin. Thus, at least functionally, the antibody appears to recognize the plasma membrane receptor for fibronectin. The antibody and its Fab fragments bound to the cell surfaces of human monocytes, tissue macrophages, and, to a lesser extent, neutrophils. It did not react with fibroblasts, lymphocytes, platelets, or erythrocytes. It bound human and guinea pig cells but did not react with rat, mouse, or hamster cells. In Western blots, this monoclonal antibody bound specifically to a polypeptide with apparent molecular weight of 110,000 and made of a single chain. The antigen recognized by A6F10 was susceptible to trypsin digestion. These observations suggest that the monoclonal antibody A6F10 is directed to the fibronectin receptor of human monocytes.