The free radical theory of O2 toxicity provides a testable explanation of the mechanism of O2's toxic effects on a biochemical and cellular level. In addition, it provides for an understanding of the array of normal antioxidant defenses of the cell and an insight to rational approaches to pharmacologic prophylaxis against clinical O2 toxicity. Neonatal animals of many species are much more resistant to the lethal effects of exposure to high concentrations of O2 than are the adult animals of the species; this increased tolerance is associated with the newborn lungs' ability to increase its normal complement of protective antioxidant enzymes during O2 exposure. Premature infants who require vigorous hyperoxic respiratory support early in life frequently develop acute and chronic lung changes compatible with pulmonary O2 toxicity, so-called bronchopulmonary dysplasia. The lung of the prematurely born may be quite ill-adapted for protecting itself against hyperoxic exposure owing to immaturity of its antioxidant defensive systems. Clinical pharmacologic stratagems designed to augment the intracellular antioxidant defensive capacity of the lung may become available in the near future, which would provide some means to prevent or ameliorate the serious lung damage associated with the clinical use of life-giving O2.