The distribution of ozone-induced injury across the ventilatory units of the lungs was determined and compared with the predicted distribution of ozone dose across the same units to evaluate dose-response relationships. Sprague-Dawley rats were exposed to either 0.98 ppm ozone 8 h/day for 90 days or to filtered air only. En bloc microdissection was used to identify and isolate in longitudinal profile the bronchiole-alveolar duct junction, first pair of alveolar duct generations, and intervening bifurcation ridge. Relative ozone dose across the ventilatory unit was estimated using the geometry of the tracheobronchial tree and the volume and surface area distribution within individual ventilatory units. This mathematical model of ozone dose demonstrated a high degree of correlation to the measured tissue injury response. The findings of this study demonstrate that microdosimetry and microtoxicology can be used to determine dose-response relationships within the ventilatory unit and to assess questions of tissue sensitivity in ozone-induced lung injury.