In this review the effects of oxidant inhalation on the pulmonary surfactant system of laboratory animals are discussed. Oxidant lung injury is a complex phenomenon with many aspects. Inhaled oxidants interact primarily with the epithelial lining fluid (ELF), a thin layer covering the epithelial cells of the lung which contains surfactant and antioxidants. In the upper airways this layer is thick and contains high levels of antioxidants. Therefore oxidant injury in this area is rare and is more common in the lower airways where the ELF is thin and contains fewer antioxidants. In the ELF oxidants can react with antioxidants or biomolecules, resulting in inactivation of the biomolecules or in the formation of even more reactive agents. Oxidation of extracellular surfactant constituents may impair its function and affect breathing. Oxidized ELF constituents may promote inflammation and edema, which will impair the surfactant system further. Animal species differences in respiratory tract anatomy, ventilatory rate, and antioxidant levels influence susceptibility to oxidants. The oxidant exposure dose dictates injury, subsequent repair processes, and tolerance induction.