The pathogenesis of O2 toxicity involves intracellular production of partially reduced O2 metabolites, which increases with O2 partial pressure. Cytotoxic O2 metabolites impair enzyme function and inhibit DNA, protein, and surfactant lipid biosynthesis. Compounds used clinically that increase O2 metabolism or that are metabolized through free radical intermediates may increase pulmonary O2 toxicity. Recent development of liposome-encapsulated and polyethylene glycol-conjugated antioxidant enzyme preparations may provide a clinically useful means of minimizing O2 toxicity and other oxidant injuries. Human pulmonary O2 toxicity is characterized initially by acute edematous lung injury followed by fibrosis and pulmonary hypertension. Functional changes due to O2 toxicity include diffusion impairment, worsening of ventilation/perfusion relationships, decreased lung compliance, and small airways dysfunction. It is likely that new data derived from molecular and cellular studies of O2 toxicity will continue to enrich the clinical atmosphere and allow more directed approaches to therapy of acute lung injuries, including ARDS.