Mammalian cells may be protected from damage by hyperoxia through the induction of enzymes that reduce destructive oxygen-free radicals. One such enzyme is superoxide dismutase, which reduces superoxide to form hydrogen peroxide and O2. We studied the concentration of this enzyme in rat alveolar macrophages exposed to 85 to 90 per cent O2 in vitro for as long as 6 days and in macrophages obtained from rats exposed to 85 to 97 per cent O2 in vivo for as long as 7 days. In no case was there an increase in superoxide dismutase in rat alveolar macrophages, despite a doubling of superoxide dismutase in whole lungs of rats exposed to 85 to 90 per cent O2 for 7 days in vivo. We concluded that the macrophage of the adult rat does not defent itself against hyperoxia by the induction of superoxide dismutase and does not participate in the increased superoxide dismutase activity of lungs of these animals exposed to hyperoxia.