Prostaglandin D2 (PGD2) lowers pulmonary arterial blood pressure without changing systemic arterial blood pressure in fetal and newborn lambs but increases pulmonary arterial pressure in older animals. We investigated the effect of PGD2 on the circulation in 15 newborn lambs, some studied intermittently from 1 to 30 days of age, with induced pulmonary arterial hypertension. PGD2 was infused intravenously in doses of 1 to 25 micrograms/kg per min. During the first 3 days of life, a 5 micrograms/kg per min infusion decreased mean pulmonary arterial pressure by 33.9%, increased mean systemic arterial pressure by 11.5% and increased cardiac output by 7.3%. After 15 days of age there was a 10.7% increase in mean pulmonary arterial pressure, a 1.8% decrease in mean systemic arterial pressure and a 6.1% increase in cardiac output. Pulmonary vascular resistance decreased by 38.2% in the first 3 days of life but increased by 9.9% after 15 days of life. With this progressive pulmonary vasoconstriction, there was systemic vasodilation with advancing age. Similar age specific effects were seen with 1 and 25 micrograms/kg per min infusions. The specificity of PGD2 for the pulmonary circulation and the attenuation of its vasodilating properties during the first week of life suggests that PGD2 may be important in the regulation of pulmonary vascular resistance and pulmonary blood flow during the immediate perinatal period.