Selective embedding processes were used to identify lesions in different regions of pulmonary acini in a histologic and ultrastructural study of the effects of a 4-hour exposure to 3 ppm ozone on rat lungs. There was a gradation of epithelial damage in acini; the severest lesions were located centrally, where there was necrosis of bronchiolar epithelium and membranous pneumonocytes. In peripheral acinar regions, membranous cells were normal; granular pneumonocytes were normal throughout. In contrast, lesions in capillary endothelium were more wide-spread. Endothelial swelling was seen in all portions of acini, but was more common centrally, and ring-like formations of endothelial membranes were found peripherally. Early stages of alveolar edema were more often seen in peripheral acinar regions and were usually accompanied by interstitial edema. These results confirm that the brunt of ozone damage is borne by centriacinar regions. Further, they highlight the need to identify portions of acini being examined ultrastructurally to avoid variable and conflicting results. The apparent separation of centriacinar epithelial damage from the peripheral location of the earliest detectable edema indicates that further exploration is needed to determine to what extent different, although overlapping, sets of pathogenetic factors might be involved.