Arachidonic acid (AA) metabolites may be important mediators in the hyperoxic lung injury process. We have previously demonstrated, in an adult model of hyperoxic lung injury, that bronchoalveolar lavage (BAL) fluid levels of AA metabolites of the cyclooxygenase pathway increase before evidence of overt injury. Nonselective inhibition with indomethacin or dexamethasone failed to ameliorate the injury process, possibly because production of prostaglandin I2 (PGI2) was suppressed. In this study, we attempted to ameliorate hyperoxic lung injury using an infusion of prostaglandin E1 (PGE1), since PGE1 has some of the potentially protective effects of PGI2. Thirty-two adult rabbits were exposed to greater than 95% oxygen; eight served as controls and 24 received PGE1 infusion (five, nine, and ten received 0.1, 0.06, and 0.03 micrograms/kg.min, respectively). At the end of the 65-h exposure period, BAL of the left lung was performed; the right was saved for light microscopy. PGE1 infusion at the 0.06 and 0.03-micrograms/kg.min doses resulted in significantly fewer polymorphonuclear leukocytes (PMN) in BAL fluid (p less than .05). However, PGE1 infusion did not significantly ameliorate the lung injury process. In summary, although PGE1 infusion inhibited the influx of PMN into the lung, treatment did not result in any significant amelioration of the hyperoxic lung injury process.