Scavenger receptors have been reported to mediate macrophage adhesion to serum-coated plastic surfaces. We report here that scavenger receptors promote the divalent cation independent adhesion of human monocytes and macrophages to surfaces coated with non-enzymatically glycated collagen IV but not to surfaces coated with native collagen IV. Ligands for scavenger receptor types I and II blocked adhesion of monocytes and macrophages to non-enzymatically glycated collagen IV but had no effect on adhesion of these cells to albumin-coated surfaces. U937 human promonocyte-like cells transfected with cDNA encoding bovine scavenger receptor I or II adhered to surfaces coated with glycated-collagen IV but not to surfaces coated with native collagen IV. A synthetic peptide homologous to the domain of bovine scavenger receptor that binds modified low density lipoproteins (residues 327-343) inhibited the adhesion of U937 cells transfected with cDNA encoding bovine scavenger receptor II to glycated collagen IV, whereas a control peptide from the alpha helical domain of scavenger receptor II (residues 121-137) had no effect on adhesion of these cells. Macrophages plated on surfaces coated with glycated collagen IV were unable to endocytose acetylated low density lipoproteins from the medium, suggesting that their scavenger receptors were occupied in binding these cells to the substrate. These findings suggest new roles for scavenger receptors in the accelerated development of vascular lesions observed in diabetics.