To determine if lung cell replication and repair might be different between younger (30-day-old) and older (60-day-old) rats, we studied polyamine and DNA biosynthesis in rats exposed to 1.0 atm oxygen for 24, 48, 56, or 72 h. By 24 h, no statistically significant changes were observed, but by 48 h, ornithine decarboxylase and putrescine increased; S-adenosylmethionine decarboxylase activity increased by 56 h in the younger rats but not in the older rats. By 72 h, spermidine, [3H]thymidine incorporation, and the labeling index of cells in the alveolar zone had increased only in the younger rats. During the first 56 h, hyperoxia inhibited DNA synthesis. We conclude that hyperoxia initially suppresses lung cell replication but subsequently, if the rat survives, there are increases in polyamine biosynthesis and cell replication that may be important for the development of oxygen tolerance.