The effects of prostacyclin (PGI2) and its metabolite, 6-keto-PGF1 alpha, on pulmonary and systemic circulations of anesthetized, unventilated fetal goats and sheep were evaluated in situ using an isolated perfused lower left lobe preparation. Results from infusions of PGI2 into the left pulmonary artery suggested dose-dependent decreases in pulmonary vascular resistance (PVR) and mean systemic arterial pressure (SAP). Two-minute infusions produced more pronounced reductions in PVR than 1-minute infusions, and fetal goats exhibited greater depressor responses to PGI2 (2-minute infusions) than fetal lambs. For every 10% decrease in mean pulmonary arterial pressure (PAP), SAP decreased by 3% in sheep receiving 1-minute infusions of PGI2. Systemic hypotensive responses and increases in heart rate were similar in both species. PGI2 appears to be a more powerful dilator of the fetal pulmonary circulation than PGE1 or PGE2; also, intrapulmonary infusions of PGI2 resulted in greater and more sustained systemic hypotensive effects than similar infusions of PGE1 and PGE2. The stable metabolite of PGI2, 6-keto-PGF1 alpha, produced attenuated pulmonary vasodilation. Since PGI2 may produce systemic hypotension, the use of this agent in treatment of persistent pulmonary hypertension should be considered with caution.