Part of the innate defence of bronchial epithelia against bacterial colonization is regulated secretion of salt, water and mucus as well as defensins and cytokines involving MAP kinase activation and alterations in early gene expression. We tested two different types of immortalized human airway epithelial cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression of c-Fos upon treatment with Staphylococcus aureus-culture supernatants from the stationary growth phase (OD_540nm = 10) or with recombinant S. aureus-hemolysins (Hla, Hlb). OD10-supernatants activated Erk-type MAP kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk-type kinase phosphorylation in S9-, but not in 16HBE14o- cells. Hlb induced Erk-activation in either cell type. Basal and stimulated levels of Erk-type MAP kinase phosphorylation were sensitive to the Mek1-inhibitor PD98059 indicating that the bacterial products activated the entire signalling cascade which co-regulates IL-8 induction and secretion. While c-Fos expression was enhanced by OD10-supernatants, Hla and Hlb in S9 cells, 16HBE14o- cells responded to OD10-supernatant and Hlb, but not to Hla. In S9 cells, PD98059 suppressed c-Fos upregulation by OD10-supernatant, Hla or Hlb indicating that c-Fos expression requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos expression by OD10-supernatant was sensitive to PD98059, while that induced by Hlb was not. This indicates that ingredients of OD10-supernatants other than Hla or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other intracellular signalling systems apart from Erk-type MAP kinases contribute to Hlb-mediated regulation of c-Fos. Thus, interaction of bacterial factors with airway epithelial cells may be highly cell type-specific.