Exposures to low levels of O3 cause epithelial and interstitial injury in the proximal alveolar region. The sequential development of this lesion caused by a simulated ambient pattern of O3 was studied by exposing Fisher 344 rats to 0.06ppm O3 overnight with an 8 hr daytime exposure having a slow increase to a peak of 0.25 ppm and then gradually decreasing back to 0.06 ppm. Animals were studied using EM morphometric techniques after 7, 21 and 90 days exposure as well as post 90 days exposures. The early changes in O3 exposed animals included increases of volumes in type II epithelium (60%), type I epithelium (16%), cellular interstitium (52%), non-cell interstitium (33%), and in alveolar macrophages (180%). The response showed a biphasic reaction with the early injury subsiding after 21 days of O3 exposure. The animals exposed for 90 days showed a 28% increase in relative volume of type I and a 42% increase in type II epithelia.