To study the early changes in the lower respiratory tract in persons exposed to periods of hyperoxia usually considered safe, we evaluated 14 normal subjects by bronchoalveolar lavage before and immediately after 16.7±1.1 hours of breathing more than 95 per cent oxygen. Hyperoxia caused a significant alveolar-capillary “leak” as detected by the presence of increased plasma albumin and transferrin in lavage fluid. These changes were reversible, as shown at repeat lavage in four subjects two weeks after oxygen administration. Hyperoxia for an average of 17 hours did not change the total number or type of lung inflammatory and immune effector cells recovered by lavage (P>0.05, all comparisons). However, alveolar macrophages from subjects exposed to oxygen released increased amounts of fibronectin (P<0.05) and alveolar-macrophage–derived growth factor for fibroblasts (P<0.01) — mediators thought to modulate fibroblast recruitment and proliferation in the alveolar wall. Thus, although some of the effects of exposure to 17 hours of more than 95 per cent oxygen are reversible, hyperoxia for even this short period lowers the structural or functional barriers that normally prevent alveolar-capillary “leak” and induces processes that can culminate in fibrosis of the alveolar wall. (N Engl J Med 1983; 309:878–83.).