This study was performed to determine whether prostaglandins play a role in the increase in pulmonary blood flow in the fetal lamb caused by an increase in oxygen tension similar to that occurring at birth. To increase fetal oxygen tension without ventilating the lungs, nine pregnant ewes with chronically instrumented fetuses were exposed to 100% oxygen at 3 atmospheres absolute pressure for 20 min in a hyperbaric chamber. This exposure increased pulmonary arterial oxygen tension in the nine fetuses from 20 ± 1 to 54 ± 9 torr. It increased pulmonary blood flow from fetal to newborn values, 31 ± 3 to 295 ± 20 ml/kg/min. It did not change pulmonary arterial pressure, 52 ± 2 torr during normoxia and 50 ± 2 torr during hyperoxia. Treating five of these fetuses with 3.2 ± 0.4 mg/kg of indomethacin during hyperbaric oxygenation did not alter these effects (Po2= 51 ± 8 torr, pulmonary blood flow = 283 ± 13 ml/kg/min, and pulmonary arterial pressure = 48 ± 2 torr). We conclude that the increase in pulmonary blood flow caused by an increase in oxygen tension in the fetus is not maintained by prostaglandins.