The basis for individual sensitivity to lung injury after exposure to inhaled particles and gases needs to be better defined. There are well-documented species differences in sensitivity to inhaled oxidant gases, and changes in susceptibility to lung injury relating to age have been demonstrated. There is a wide variability in the sensitivity of specific cells to injury by various oxidants and particulates. While the lung has a number of common ways of responding to all types of injury, significant variations occur in terms of which cells respond and which sites within the lung show the major response. There are also differences in the time course of the response. Variations in cell distributions, changes in mucus thickness, and differences in the dose delivered to specific sites are all important in determining the magnitude of injury that occurs. The bronchiolar-alveolar duct junction area is one of the primary sites of injury caused by strong oxidant gases that are inhaled in relatively low concentrations. This is thought to relate to a balance between proximal protective and clearance mechanisms and the dilution of the gas as it moves distally, which reduces the dose delivered to the alveolar region of the lung. The airway anatomy and ventilation patterns of the animal are important in determining a site-specific dose. These factors combine with differences in cell sensitivity to help define why some species or individuals are uniquely sensitive to the inhalation of toxic gases and particles.