We report here that human macrophages bind Escherichia coli by recognizing bacterial lipopolysaccharide (LPS). Purified LPS was inserted into erythrocyte membranes, and the resulting LPS-coated red cells were bound by macrophages with the same temperature and cation dependence as observed for E. coli. When receptors for LPS were withdrawn from the plasma membrane by spreading the macrophages on LPS-coated surfaces, the binding of E. coli was blocked. We have also identified the receptors on macrophages that recognize LPS. Macrophages express three structurally homologous cell surface proteins, CR3, lymphocyte function-associated antigen (LFA-1), and p150,95. We used surface-bound monoclonal antireceptor antibodies to selectively remove these proteins from the apical surface of macrophages. We found that each of these proteins mediated the binding of E. coli to macrophages.