The effects of hyperoxia on physiological responses, pathological lung lesions detected noninvasively by proton magnetic resonance imaging (MRI), and the oxygen free radical defense enzymes were measured in Cu-deficient rats. Exposure to 85% oxygen seemed to impose a stress on the whole animal as indicated by two physiological responses, decreased food intake and decreased body weight of ad libitum-fed rats. However, all rats exposed to 85% oxygen, including the Cu-deficient group, were able to survive 1 wk of hyperoxia exposure. The target organ specificity for hyperoxia exposure was in the lung as indicated by the increased lung:body weight ratio in all hyperoxia-exposed rats regardless of dietary treatment. All dietary treatment groups exposed to hyperoxia had a similar increase in lung:body weight ratio, but none of the hyperoxia-exposed rats had MRI-detectable lung damage. After 7 d of hyperoxia exposure, all dietary treatment groups, including the Cu-deficient rats, had increased activity of lung CuZn-superoxide dismutase (CuZnSOD), but changes in CuZnSOD activity were not related to lung Cu or Zn concentrations. We propose that the ability to increase CuZnSOD activity is the most important factor of the enzymatic oxygen free radical defense system for protection against hyperoxia-induced lung damage detected by MRI. Even though lung Cu concentration was decreased in Cu deficiency, it seems that Cu-deficient rats are still able to increase lung CuZnSOD activity in response to 85% oxygen exposure.