To study the effect of chronic hyperoxia and hypoxia on pneumonectomy-induced compensatory lung growth, 4-week-old male rats were randomly divided into 4 groups: pneumonectomy controls, pneumonectomy hyperoxic group (fraction of ambient oxygen [FO2] 0.35), pneumonectomy hypoxic group (FO2 0.14), and unoperated controls. After 2 weeks, somatic growth of pneumonectomy hypoxic rats was diminished. Compared to unoperated controls, lung weight increased in all pneumonectomy groups but lung volume increased only in pneumonectomy control and pneumonectomy hypoxic rats. Alveolar surface area also increased in pneumonectomy control and pneumonectomy hypoxic animals. Lung weight, volume, and alveolar surface area in pneumonectomy hypoxic rats were also significantly higher than in pneumonectomy hyperoxic rats. When lung weight, volume, alveolar surface area, and total number of alveoli were normalized for body weight, the values were significantly higher in pneumonectomized hypoxic rats than in the pneumonectomy control and pneumonectomy hyperoxic groups. Maximal increase in volume occurred in the post-caval and upper lobes in all pneumonectomized groups. Compared to unoperated rats, mean linear intercept also increased in the post-caval lobe in all pneumonectomized groups. The results suggest that 2 weeks after left pneumonectomy, compensatory lung response is incomplete. Chronic hypoxia enhances, whereas hyperoxia inhibits compensatory lung growth. The post-caval and upper lobes respond more and the lower lobe responds less following left pneumonectomy in both hypoxia and hyperoxia.