Incubation of normal or thioglycollate-elicited mouse peritoneal macrophages with 2-deoxy-D-glucose (2-dG) inhibits the capacity of these macrophages to phagocytize IgG- or complement-coated particles via their Fc and C3 receptors. 2-dG has no inhibitory effect on the capacity of these macrophages to phagocytize latex or zymosan particles, which are ingested in the absence of specific opsonins, and it does not inhibit binding of IgG- or C3-coated particles to their respective receptors on the macrophage's plasma membrane. 2-dG exerts its inhibitory effect on the macrophage and not on the opsonized particle. The inhibition is independent of particle size, occurs within 15-30 min of addition of this glucose analogue to the medium at 37 degrees C, cannot be overcome by supra-agglutinating amounts of opsonizing antibody, and is completely reversible by substitution of 5.5 mM glucose for 50 mM 2-dG in the medium. Addition of equimolar amounts of glucose or mannose, but not of fructose, galactose, fucose, or glucosamine, to medium containing 50 mM 2-dG results in substantial reversal of the inhibitory effect of 2-dG on Fc and C3 receptor mediated phagocytosis.