Elevated concentrations of eicosanoids have been reported in bronchoalveolar lavage fluid (BALF) and blood of infants with persistent pulmonary hypertension (PPHN), thereby indicating their potential role in its pathophysiology. Extracorporeal membrane oxygenation (ECMO) has improved the outcome in selected infants with PPHN. We hypothesized that ECMO, by alleviating lung injury, would be associated with decreased eicosanoid production and clinical improvement. Twenty-two newborns with PPHN treated with either ECMO or conventional means were studied. Concentrations of TxB2, 6-keto-PGF1 alpha, PGD2, PGE2, LTB4, and LTE4 were serially measured in BALF. Elevated concentrations of all eicosanoids measured were observed in all infants with PPHN at the initiation of ECMO. Eicosanoid concentrations decreased in all infants with a good clinical outcome after ECMO, but they remained elevated in those with a poor outcome. In patients with less severe PPHN, not requiring ECMO, lower concentrations of eicosanoids were observed at initiation of therapy. Eicosanoid levels increased or did not change over the course of conventional treatment. We conclude that eicosanoids are present in high concentrations in infants with PPHN. Iatrogenic factors, including oxygen and barotrauma, appear to correlate with their concentrations. Removal of these factors is associated with decreased production of mediators and clinical improvement.