Staphylococcus aureus infections are often life-threatening. Relatively little is known about the host response to these infections, in particular, the implication of apoptosis induced by this microorganism. In this study, we have shown that S. aureus was cytotoxic to J774A.1 cell, a murine macrophage cell line. The cell death mediated by S. aureus occurred through apoptosis, as shown by increase in the proportion of fragmented host cell DNA. Although phagocytosis and NO production had important role in the induction of apoptosis, the contact between bacteria and host cells was not essential for this pathway. A certain bacterial product could also induce typical caspase-dependent apoptosis of J774A.1 cell. It is expected that new interpretation may be possible to host-parasite relationship based on these results.