We examined the effects of ozone (O₃) and endogenous antioxidant transport on canine peripheral airway function, central airway function, epithelial integrity, and inflammation. Dogs were either untreated or pretreated with probenecid (an anion-transport inhibitor) and exposed for 6 h to 0.2 parts/million O₃. Peripheral airway resistance (Rpa) and reactivity (Rpa) were monitored in three sublobar locations before and after exposure to either air or O₃. Pulmonary resistance and transepithelial potential difference in trachea and bronchus were also recorded. Bronchoalveolar lavage fluid (BALF) was collected before, during, and after exposure. O₃ increased Rpa and Rpa only in probenecid-treated dogs and in a location-dependent fashion. Pulmonary resistance and potential difference in bronchus increased after O₃ exposure regardless of treatment. O₃ markedly increased BALF neutrophils only in untreated dogs. With the exception of hexanal, O₃ did not alter any BALF constituent examined. Probenecid reduced BALF ascorbate, BALF protein, and plasma urate. We conclude that 1) a 6-h exposure to 0.2 parts/million O₃ represents a subthreshold stimulus in relation to its effects on peripheral airway function in dogs, 2) antioxidant transport contributes to the maintenance of normal airway tone and reactivity under conditions of oxidant stress, 3) O₃-induced changes in Rpa and Rpa are dependent on location, and 4) peripheral airway hyperreactivity and inflammation reflect independent responses to O₃ exposure. Finally, although anion transport mitigates the effect of O₃ on peripheral airway function, it contributes to the development of airway inflammation and may represent a possible target for anti-inflammatory prevention or therapy.