The effects of bacterial neuraminidase on production of hydrogen peroxide (H2O2) and killing of Staphylococcus aureus by human polymorphonuclear leukocytes (PMN) were studied. The concentration of H2O2 was measured by the disappearance of scopoletin fluorescence in the presence of horseradish peroxidase. The results indicated that desialylation of human PMN inhibited the stimulation of H2O2 production during phagocytosis. It also markedly impaired the killing of S. aureus. Impaired killing of S. aureus by desialylated PMN was due to impaired intracellular killing rather than defective phagocytosis.