Because fetal rat lungs have lower baseline levels of both surfactant and antioxidant enzymes than full-term newborn rats, we questioned whether prematurely delivered rats might be more susceptible to O2 toxicity than those born at term. In the present studies, prematurely delivered rats (gestational d 21 of 22) and full-term rat pups were simultaneously put in > 95% O2 after birth. Surprisingly, we found that the preterm rats were not more susceptible to O2-induced lung damage and lethality than full-term newborns, but, in fact, the composite percentage of survival was even greater in the preterm pups from 7 to 9 d in hyperoxia and were similar thereafter up to 14 d in high O2. In addition, the preterm rats showed significantly decreased lung wet/dry weight ratios and consistently less severe pathologic evidence of pulmonary edema compared with term rats at 6 and 8 d of O2 exposure. The premature pups demonstrated the capability of inducing pulmonary antioxidant enzyme responses to hyperoxia by 3 d, and had significantly elevated copper-zinc superoxide dismutase, catalase, and glutathione peroxidase activities (and lung surfactant contents) at 6 d of O2 exposure compared with the term rats in O2. The rates of lung total O2 consumption and cyanide-resistant O2 consumption at d 6 in hyperoxia were not different for preterm versus term pups. Although the basis for the transiently improved survival and decreased evidence of pulmonary O2 toxicity in the preterm rats is presently unknown, these findings clearly indicate that premature animals of at least one species are equally able to induce protective lung antioxidant enzymes and surfactant responses to hyperoxia as full-term newborn animals.