Ozone (O(3)) is among the most reactive environmental oxidant pollutants to which cutaneous tissues are exposed. O(3) exposure has been shown to induce antioxidant depletion as well as the oxidation of lipids and proteins within the outermost skin layer, the stratum corneum. However, relatively little is known regarding the potential effects of O(3) on the cellular constituents of the underlying skin epidermis and dermis. In the present study, hairless mice exposed for 6 h to 0.8 ppm O(3) showed increases in lipid peroxidation, as quantitated by increases in 4-hydroxynonenal-protein adducts. O(3) exposure caused an induction of the stress proteins HSP27 and heme oxygenase-1 (HO-1), starting at 6 h and increasing up to 18 h after O(3) exposure. This was accompanied by an increase in matrix metalloproteinase-9 (MMP-9) mRNA and activity levels, indicative of possible injurious-reparative processes. Collectively, our data demonstrate that skin exposure to O(3) not only affects antioxidant levels and oxidation markers in the outermost stratum corneum layer, but also induces cellular stress responses in the deeper cellular layers of the skin.