We report that phagocytosis by human neutrophils of Con A-treated erythrocytes (E-Con A) and nonopsonized Escherichia coli with mannose-binding adhesions is mediated by the Fc gamma receptor bearing the 3G8 epitope. Modulation of Fc receptors by pretreating with aggregated-IgG or with 3G8 anti-Fc gamma receptor mAb markedly inhibited internalization of E-Con A and E. coli without altering their cell surface attachment. Phagocytosis of these probes was specifically blocked by alpha-methylmannoside and D-mannose and not by other monosaccharides. Thus, recognition of E-Con A and E. coli by the Fc receptor is dependent upon the mannose-specific interaction with lectin or lectin-like adhesions. These data demonstrate that ligands other than the classical IgG opsonins can bind to classical immune receptors for IgG through lectin-carbohydrate interactions.