SummaryWe administered sodium meclofenamate, a prostaglandin synthetase inhibitor, to 15 piglets (ages 5-70 d) to test the hypothesis that endogenous prostaglandin pulmonary vasodilators influence total pulmonary resistance under both normoxic and hypoxic conditions. No significant differences in hemodynamic measurements were found between the control group and drug-treated animals more than 12-d-old. When six experimental animals less than 12 d of age were compared with six age-matched controls, meclofenamate produced a small but significant increase in mean pulmonary artery pressure (110 ± 9versus97 ± 10%,P< 0.05) and total pulmonary resistance (135 ± 23versus102 ± 12%,P< 0.03). The magnitude of the change in total pulmonary resistance produced by 2 mg/kg of meclofenamate during normoxia correlated inversely with postnatal age (r= 0.83,P< 0.01). Individual changes in pulmonary hemodynamics produced by acute hypoxia after meclofenamate treatment were the same as pretreatment values and were similar in both young and older animals.