The ability of S. aureus to resist phagocytosis by polymorphonuclear leukocytes (PMN) is thought to be an important virulence factor for this microorganism. We have studied the effect of 3 major cell wall components of S. aureus, peptidoglycan, protein A, and teichoic acid, on PMN function. Phagocytosis and chemotaxis were both inhibited by prior incubation of PMN with peptidoglycan. This effect was dose- and time-related; incubation with as little as 2.5 micrograms/ml for 30 min produced a discernible suppressive effect. Suppression of PMN function was independent of the presence of human serum but was abolished by rabbit antiserum to peptidoglycan. Addition of peptidoglycan to PMN stimulated a prolonged chemiluminescence response that was greater when the peptidoglycan was first incubated in normal serum, perhaps reflection opsonization of this particulate material. Although protein A also suppressed phagocytic and chemotactic capabilities of PMN, this effect was observed only in the presence of serum and was eliminated by absorbing Ig. Centrifugation of the serum + protein A mixture showed that the suppressive effect was contained in the precipitated sediment. Complexes of Ig alone were not suppressive. Teichoic acid in concentrations less than or equal to 100 micrograms/ml had no adverse effect on PMN function. These studies describe ways in which peptidoglycan and protein A may interfere with phagocytosis and chemotaxis of human PMN, thus giving evidence for the role of these cell wall components as virulence factors.