Protein A, a component of the outer layer of the cell wall of Staphylococcus aureus impairs opsonization by serum complement and thereby delays phagocytosis by polymorphonuclear leukocytes. Two antibiotics with modes of action on bacterial protein biosynthesis, have been used at sub-growth inhibitory concentrations to regulate the production of protein A. Both clindamycin and fusidic acid (either at 1/2 or 1/4 MIC) reduced the amount of protein A on the cell surface. Such drug-grown cells became more susceptible to phagocytic uptake and killing. Chemiluminescence (CL) of PMN when presented with preopsonized drug-grown staphylococci was potentiated and correlated with the enhanced phagocytosis seen earlier. The level of CL appeared to depend upon the amount of human serum used to opsonize the bacteria. Reduced protein A content on the cell surface probably resulted in the exposure of a greater number of receptor sites for C3b, rendering the bacterium more susceptible to attachment and ingestion by the polymorphonuclear leukocyte.