Prolonged exposure to hyperoxia can result in significant lung injury, although newborn animals are more oxygen-tolerant than adults. Mechanisms affording tolerance to the newborn are incompletely understood. This study examined the hypothesis that eicosanoids play a significant role in newborn oxygen tolerance. One litter of term newborn albino rabbits and 15 adult rabbits were exposed to 65 hours of greater than 95% O2. An additional litter of newborns served as a normoxic control. Normoxic newborn rabbits had very high quantities of 6-keto-PGF1a and low TXB2 in bronchoalveolar lavage (BAL) fluid. Sixty-five hours of oxygen exposure in newborn rabbits produced no evidence of lung injury on light microscopy, 97% of BAL white cells were alveolar macrophages and BAL protein was low. An equal period of oxygen exposure produced significant lung injury in adult rabbits. BAL fluid from oxygen-injured adults contained a 17-fold greater percentage of PMN and 16-fold higher protein than oxygen-exposed newborns. Hyperoxic adults had significantly lower 6-keto-PGF1a, and significantly higher LTB4 and LTC4 in BAL compared to hyperoxic newborns. This study confirms the hypothesis of relative oxygen tolerance in newborn rabbits compared to adults, and suggests that this tolerance may have been afforded by higher pulmonary levels of the protective prostacyclin metabolite.