To explore the molecular basis for the ability of aggregated IgG to block the phagocytosis by human polymorphonuclear leukocytes of Con A-opsonized E and nonopsonized Escherichia coli with mannose-binding adhesins, we examined specific aspects of the glycoprotein structure of both the 40- to 43-kDa receptor for the Fc portion of IgG (FcγRII) and the 50- to 78-kDa receptor for the Fc portion of IgG (FcγRIII(PMN)) from human polymorphonuclear leukocytes. FcγRIII(PMN) isolated by both mAb and ligand affinity chromatography, but not FcγRII, binds Con A in Western blots. This binding is specifically inhibitable by α-methylmannoside. Digestion of FcγRIII(PMN) by recombinant endoglycosidase H, which is specific for high mannose-type (Con A-binding) oligosaccharides, alters the epitope recognized by mAb 3G8 in or near the IgG ligand-binding site of the receptor. Similarly, the ability of FcγRIII(PMN) to bind human IgG ligand is sensitive to endoglycosidase H digestion. Our data indicate that ligands other than the classical IgG opsonins can bind to human FcγRIII(PMN) per se through lectin-carbohydrate interactions. Furthermore, FcγRIII(PMN) contains a high mannose type oligosaccharide chain which contributes importantly to the integrity of the classical IgG ligand-binding site. Thus, specific glycosylations of the receptor are important for both classical and nonclassical engagement of FcγRIII and may play a role in determining the properties of the ligand-binding site.