The pulmonary vascular effects of the newly discovered prostacyclin metabolite, 6-keto-prostaglandin E1 (6-keto-PGE1) were investigated in the intact-chest cat. Intrapulmonary injections of 6-keto-PGE1 decreased lobar arterial prefusion pressure in a dose-dependent manner. Inasmuch as pulmonary blood flow was held constant, and left atrial pressure was unchanged, the fall in lobar vascular resistance. Decreases in lobar arterial pressure in response to 6-keto-PGE1 were greatly enhanced when tone in the pulmonary vascular bed was increased by infusion of a stable prostaglandin endoperoxide analog. 6-Keto-PGE1 decreased systemic arterial pressure increased cardiac output and reduced systemic vascular resistance in the cat. Decreases in systemic arterial pressure and systemic vascular resistance were similar when 6-keto-PGE1 was injected into the right or left atrium, suggesting that the substance is not converted to less active metabolites in passage through the feline pulmonary vascular bed. 6-Keto-PGE1 reversed the hypertensive effects of ADP in the pulmonary vascular bed suggesting this agent may inhibit ADP-induced platelet aggregation in small intrapulmonary vessels. These data indicate that 6-keto-PGE1 has marked vasodilator activity in the feline pulmonary and systemic vascular beds and since 6-keto-PGE1 is not inactivated in the lung it could serve as a circulating hormone.