The effects of prostacyclin (PGI 2) and its metabolite, 6-keto-PGF(1α), 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 PGI 2 into the left pulmonary artery suggested dose-dependent decreases in pulmonary vascular resistance (PVR) and mean systemic arterial pressure (S̄ĀP̄). Two-minute infusions produced more pronounced reductions in PVR than 1-minute infusions, and fetal goats exhibited greater depressor responses to PGI 2 (2-minute infusions) than fetal lambs. For every 10% decrease in mean pulmonary arterial pressure (P̄ĀP̄), S̄ĀP̄ decreased by 3% in sheep receiving 1-minute infusions of PGI 2. Systemic hypotensive responses and increases in heart rate were similar in both species. PGI 2 appears to be a more powerful dilator of the fetal pulmonary circulation than PGE 1 or PGE 2; also, intrapulmonary infusions of PGI 2 resulted in greater and more sustained systemic hypotensive effects than similar infusions of PGE 1 and PGE 2. The stable metabolite of PGI 2, 6-keto-PGF(1α), produced attenuated pulmonary vasodilation. Since PGI 2 may produce systemic hypotension, the use of this agent in treatment of persistent pulmonary hypertension should be considered with caution.