One of the more fascinating aspects of in vivo research on pulmonary O2 toxicity is the striking difference in the response of the neonatal versus the adult animal to hyperoxia. In general, neonatal animals are much more resistant to the characteristic O2-induced lung pathology seen in adult animals in hyperoxia. Neonatal animals are also able to rapidly mount a protective lung biochemical response to high O2 exposure [increased pulmonary antioxidant enzyme (AOE) activities], an adaptive response which adult animals have lost the ability to manifest in greater than 95% O2. This review focuses on the disparate AOE responses of the neonatal versus adult animal in hyperoxia. It also explores other possible explanations for the striking O2 tolerance of young versus adult animals, including comparative O2 free radical production rates, inflammatory cell responses, lung lipid composition, repair capabilities, etc. Discussion also centers on a less well studied toxic complication associated with hyperoxic exposure in the neonatal animal, i.e., the marked inhibitory effect of O2 exposure on normal lung growth and development of an alveolarized lung with an expanded respiratory exchange surface area. Finally, effective experimental means of protecting adult (and neonatal) animals from pulmonary O2 toxicity are reviewed. A closing section considers the enlightening new information that molecular biology has revealed about the regulation of AOE gene expression during normal development and under conditions of hyperoxidant challenge.