Objective and Design. To examine the role of macrophages in the neutrophil migration induced by staphylococcal enterotoxin type A (SEA) in mice. Materials and Methods: Peritoneal macrophages were harvested from male Swiss mice pre-treated with thioglycollate. After adhering to plastic tissue culture dishes, the cells were washed and incubated with RPMI or SEA (0.62-2.5 mug/ml) and washed again prior to further incubation with RPMI alone. The medium was then collected, sterilized and assayed for promigratory activity in the mouse peritoneal cavity. Results: Mouse macrophage monolayers stimulated with SEA secreted a thermolabile neutrophil chemotactic component (MNCC-SEA) with a molecular mass > 100 kDa (by ultrafiltration). This release was dose- and lime-dependent and was inhibited by dexamethasone but not by indomethacin or BW755C. Dexamethasone, indomethacin, BWA4C, BW755C, BN52021, cimetidine and SR48968 had no effect on the neutrophil migration induced by MNCC-SEA while capsaicin and SR140333 reduced this phenomenon. Conclusions: Macrophages play a key role in the neutrophil recruitment induced by SEA probably by releasing an MNCC-SEA that presumably induces neutrophil migration via a mechanism mediated by substance P.504206212