Prostaglandin D2 (PGD2) is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels. Pulmonary vascular responses of anesthetized fetal and adult goats and newborn lambs to PGD2 were evaluated in situ by means of an isolated perfused lower left lobe preparation. These experiments indicate that PGD2 is a pulmonary vasodilator in fetal goats, both a pulmonary vasodilator and vasoconstrictor in newborn lambs depending on the dose used, and a pulmonary vasoconstrictor in adult goats. Evidence is presented of an age-related change in pulmonary vascular response to prostaglandins. The responses of the pulmonary vasculature are dose dependent; however, there is not a significant dose-dependent relationship for systemic arterial pressure or heart rate with intrapulmonary infusions of PGD2. The inhibition of prostaglandin synthesis potentiates the pulmonary response to PGD2 in fetal goats. In contrast with other prostaglandins, PGI2, PGE2, and PGE1, which dilate both the fetal pulmonary and systemic circulations, PGD2 has minimal action on the systemic circulation over a wide range of doses.