Asbestos fibres are bio persistent particles, which are capable of stimulating chronic inflammatory responses in the pleura of exposed individuals. Exposure of pleural mesothelial cells, the progenitor cell of malignant mesothelioma (MM), to asbestos induces an array of cellular responses. The present studies investigated if the p38 mitogen activated protein kinase cascade was induced under asbestos exposed conditions. p38 plays a vital role in the response to stressful stimuli and enables entry to an inflammatory state characterised by cytokine production. Western blot and in vitro kinase assays showed increases in both dual phosphorylation and actual activity of p38 following exposure to both fibrous and non-fibrous (milled) crocidolite, in contrast, polystyrene beads and iron (III) oxide had no such effects. In common with other asbestos-induced events this was shown to be an oxidative stress-sensitive effect as pre-incubation with either N-acetyl-L- cysteine (NAC) or -tocopherol (vitamin E) ameliorated the effect. The present studies show that p38 activity is important for crocidolite-induced AP-1 DNA binding as an inhibitor of p38, SB203580, reduced this activity. Crocidolite-induced cytotoxicity was also reduced with SB203580, indicating a role for p38 in asbestos mediated cell death. Our studies suggest that p38 activity could be a crucial factor in the chronic immune response elicited by asbestos and may represent a target for future pharmacological intervention.