Pulmonary hypertension is a major source of morbidity and mortality in infants born with congenital diaphragmatic hernia (CDH). Increased pulmonary vascular resistance leads to right-to-left shunting, which is evident as decreases in the PaO 2 measured in postductal arterial blood. Thromboxane A 2 (TXA 2), a vasoconstrictor, and prostacyclin (prostaglandin I 2, PGI 2), a vasodilator, have been studied as possible mediators of pulmonary hypertension in certain conditions of the newborn, including congenital diaphragmatic hernia (CDH). The goal of our study was to determine the association of TXA 2 and PGI 2 levels with hypoxemia in infants born with CDH. Eleven newborn infants with severe respiratory insufficiency (birth weight 2.0–4.1 kg; gestational age 32–42 weeks) were studied 0–5 days after surgical repair of CDH. Umbilical artery samples were collected for arterial blood gas determinations and radioimmunoassay of thromboxane B 2 (TXB 2) and 6-keto prostaglandin F 1α (6-keto-PGF 1α), stable metabolites of TXA 2 and PGI 2, respectively. Postductal arterial hypoxemia (reflected by a low a-A ratio, the ratio of oxygen tension in arterial blood to that in the alveolus) was associated with increases in TXB 2 ( r = −0.71, P = 0.004) and 6-keto-PGF 1 ( r = −0.65, P = 0.017). The a-A ratio also correlated inversely with TXB 2/6-keto-PGF 1α ( r = −0.50, P = 0.01), suggesting an increased influence of the vasoconstrictor TXA 2. Increases in arterial carbon dioxide tension (PaCO 2) were associated with the highest levels of TXB 2 ( r = 0.70, P = 0.01) and 6-keto-PGF 1α ( r = 0.85, P = 0.001), but had no correlation with TXB 2/6-keto-PGF 1α ( r = 0.04, P = 0.85). Low pH was associated with high postductal TXB 2 ( r = −0.49, P = 0.01) and 6-keto-PGF 1α ( r = −0.67, P = 0.001), but not with TXB 2/6-keto-PGF 1α ( r = 0.02, P = 0.90). Stepwise multiple regression showed that a-A ratio and PaCO 2, but not postductal arterial pH, had significant independent effects on TXB 2 and 6-keto-PGF 1α. Patients who died had higher mean TXB 2 and 6-keto-PGF 1α levels than survivors. Increased levels of TXA 2 and PGI 2 appear to be associated with postductal arterial hypoxemia and hypercarbia in CDH. These observations support the hypothesis that activation of the arachidonic acid cascade and the formation and release of TXA 2 and PGI 2 are among the biochemical influences that produce pulmonary hypertension in CDH.