The immediate effect on the pulmonary circulation of reoxygenation with either room air or 100% O2was studied in newborn piglets. Hypoxemia was induced by ventilation with 8% O2until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with either room air (n= 9) or 100% O2(n= 9). Mean pulmonary artery pressure increased during hypoxemia (p= 0.012). After 5 min of reoxygenation, pulmonary artery pressure increased further from 24 ± 2 mm Hg at the end of hypoxemia to 35 ± 3 mm Hg (p= 0.0077versusbaseline) in the room air group and from 27 ± 3 mm Hg at the end of hypoxemia to 30 ± 2 mm Hg (p= 0.011versusbaseline) in the O2group (NS between groups). Pulmonary vascular resistance index increased (p= 0.0005) during hypoxemia. During early reoxygenation pulmonary vascular resistance index decreased rapidly to values comparable to baseline within 5 min of reoxygenation in both groups (NS between groups). Plasma endothelin-1 (ET-1) decreased during hypoxemia from 1.5 ± 0.1 ng/L at baseline to 1.2 ± 0.1 ng/L at the end of hypoxemia (p= 0.003). After 30 min of reoxygenation plasma ET-1 increased to 1.8 ± 0.3 and 1.5 ± 0.2 ng/L in the room air and O2groups, respectively (p= 0.0077 in each groupversusend hypoxemia; NS between groups). We conclude that hypoxemic pulmonary hypertension and plasma ET-1 normalizes as quickly when reoxygenation is performed with room air as with 100% O2in this hypoxia model with newborn piglets.