Tropospheric ozone (O 3), a major environmental component of photochemical urban air pollution formed from atmospheric pollutants, is detrimental to health because of its oxidant and toxic properties (reviewed in Mudway and Kelly 2000). Depending on geographical and seasonal factors, O 3 baseline concentration naturally occurring in the troposphere varies between 0.02 and 0.04 ppm (part per million), which is only three or five times below deleterious concentrations. Exposure to this toxic gas is more and more frequent within and around urban areas, and contributes significantly to increase morbidity in human populations (Gryparis et al. 2004; Chang et al. 2010; Cooper et al. 2010). Although most reports on the effects of O 3 have focused on respiratory tract inflammation and dysfunctions (reviewed in Mudway and Kelly 2000), there is accumulating evidence that supra-ambient levels of O 3 could affect the CNS, resulting not only in neuronal changes in the brainstem (Chen et al. 2003) but also in memory impairment (Avila-Costa et al. 1999), disruption of sleep patterns (Paz and Bazan-Perkins 1992), reduced cognitive performance (Tepper and Weiss 1986; Chen and Schwartz 2009), alteration of social behavior (Musi et al. 1994), and motor activity deficits (Dorado-Martínez et al. 2001). However, the mechanisms through which O 3 exerts toxic effects on the CNS remain poorly understood; and the possible involvement of a neural pathway linking respiratory tract inflammation to CNS dysfunctions has never been examined. The current study has been designed to establish the pattern of central neuronal activation induced by O 3 inhalation. In this context, c-Fos and Fos-B immunoreactive (Fos-ir) staining was used to reveal activated neurons (reviewed in Kovács 1998).