Pulmonary superoxide dismutase (SOD) activity was determined for various groups of human fetuses, infants, and adults. Enzyme activity was found to increase with age from a low of 17 ± 1 units/nig DNA in fetal lung to 49 ± 6 units/nig DNA in infant lung and finally to 110.2 ± 14.8 units/mg DNA in adult lung (P<0.05). No difference in lung SOD activity was demonstrated between normal infants and those with idiopathic respiratory distress/hyaline membrane disease (IRDS/HMD). No significant differences in SOD activity were found among all the samples of infant blood. Adult blood samples, however, contained significantly greater SOD activity both in terms of heme concentration and volume of whole blood (P<0.05). SOD activity in lung tissue from both rats and rabbits was also found to increase with age from a low value in fetal animals to a maximum activity in adults (P<0.05). Exposure of New Zealand White rabbits, prematurely delivered by caesarian section, to 80% oxygen for 24 hr resulted in a 42% increase in lung SOD activity. Similarly, 7-day-old Sprague-Dawley rats exposed to 85% oxygen for 24 hr showed a 43% increase in pulmonary SOD activity. No increase in pulmonary SOD was observed when adult rats were exposed to 85% oxygen for 24 hr. The effect of hyperoxia on SOD activity in excised lung was investigated. Rat lung, incubated in either heparinized whole blood or in plasma and exposed to 100% oxygen, showed a 30% increase in SOD activity after 2 hr. This capacity of lung tissue to respond to hyperoxiain vitrowith increased SOD activity was age dependent. The maximum increase in SOD activity was seen with lungs from 10–12-day-old rats. The oxygen-stimulated increase in lung SOD activity disappeared at about 19–20 days of age.