Ambient ozone (O(3)) is a commonly encountered environmental air pollutant with considerable impact on public health. Many other inhaled environmental toxicants can substantially affect pulmonary immune responses. Therefore, it is of considerable interest to better understand the complex interaction between environmental airway irritants and immunologically based human disease. The innate immune system represents the first line of defense against microbial pathogens. Intact innate immunity requires maintenance of an intact barrier to interface with the external environment, effective phagocytosis of microbial pathogens, and precise detection of pathogen-associated molecular patterns. We use ambient O(3) as a model to highlight the importance of understanding the role of exposure to ubiquitous air toxins and regulation of basic immune function. Inhalation of O(3) is associated with impaired antibacterial host defense, in part related to disruption of epithelial barrier and effective phagocytosis of pathogens. The functional response to ambient O(3) seems to be dependent on many components of the innate immune signaling. In this article, we review the complex interaction between inhalation of O(3) and pulmonary innate immunity.