Animals exposed to 85 per cent O2 for 5 or more days acquire the ability to survive for prolonged periods in 100 per cent O2. The basis of this acquired" tolerance" is poorly understood, but it has been proposed to be related to biochemical changes occurring in the lung cells. In order to quantify the structural changes that occur in the lungs of oxygen-adapted rats, rats were exposed to 85 per cent O2 for 7 days and then studied using morphometric techniques. The oxygen-adapted rats had a normal number of alveolar type I epithelial cells and a moderate increase in the number of alveolar type II cells. The alveolar type I epithelium was intact over the entire alveolar surface and appeared to have a normal ultrastructure, whereas alveolar type II cells demonstrated occasional changes in mitochondrial structure. In the interstitial compartment, there was a large increase in the number of interstitial cells and a significant increase in the noncellular components of the interstitium. The major area of pulmonary damage occurred in the vascular compartment, where entire segments of the capillary bed were lost and the total number of endothelial cells decreased by 45 per cent. A significant change in pulmonary vascular hemodynamics was suggested by a 49 per cent decrease in total capillary lumen volume and a decrease in the hematocrit of blood in the pulmonary capillary lumen to 57 per cent of the value found in aortic blood.