We evaluate the effect of two macrolide drugs (miocamycin and erythromycin) on human neutrophil cells (PMNs) against S. aureus strains. We studied: a) S. aureus pre-treatment effect, using subinhibitory concentrations of the two drugs, on its phagocytosis by human PMN's; b) effect of the drugs on superoxide production by PMN's; c) intracellular activity of the two drugs against S. aureus. Prior treatment of S. aureus with subinhibitory concentrations (25% of the MIC) increases significantly the phagocytosis of opsonized bacteria by human PMN's. Using non-opsonized bacteria, the registered effect was only statistically significant for miocamycin. Pre-incubation of human PMN's with 1, 10 and 25 mg/L concentrations of each drug did not influence superoxide production of the cells. Both drugs showed slight intracellular activity against S. aureus inside human PMN's, although this only achieves statistically significant difference with higher concentrations (25 mg/L) of miocamycin. In summary, both drugs influence directly human PMN's phagocytosis of S. aureus, changing the opsonic requirements of the microorganism. At therapeutic levels, neither erythromycin nor miocamycin hampered phagocytic and bactericidal mechanisms of human PMN's. At higher concentration, miocamycin showed good intracellular activity against S. aureus.