Whereas guinea pigs have advanced prenatal morphological lung development, their surfactant development is not "precocious" compared with other small laboratory animals. To investigate whether maturation of the antioxidant enzyme (AOE) system coincides more closely with surfactant development or with morphological maturation, we assayed fetal guinea pig lungs at gestational days 49-69 for superoxide dismutase, catalase, and glutathione peroxidase activities. We found that elevations in pulmonary AOE occurred in parallel with increases in surfactant during the final 10-15% of gestation. Since newborn guinea pigs behave more like adult animals in their relative intolerance to hyperoxia, we explored whether prematurely delivered guinea pigs would tolerate high O2 exposure better than full-term newborns. We found that prematures have markedly improved hyperoxic tolerance compared with newborns (time at which 50% of animals died in greater than 95% O2, 6.4 days vs. 4.5 days, respectively, P less than 0.05); and (unlike newborns) premature pups are capable of mounting an elevated AOE response to hyperoxic challenge. Thus premature guinea pigs behave more like full-term newborns of other species in respect to hyperoxic tolerance, an additional precocious feature of guinea pig development.