The ability of the kidney to release prostacyclin (PGI2) under direct stimulation with exogenous angiotensin II was studied in the pentobarbital-anesthetized dog. We assayed for prostacyclin-like activity in systemic arterial blood by continuously monitoring platelet aggregation in vivo and with the blood-bathed bovine coronary artery, which relaxes to prostacyclin. This parallel bioassay allows detection of small amounts of prostacyclinlike activity released into the systemic circulation. Angiotensin II, infused at a rate of 10 or 20 ng/kg/min into the renal artery inhibited platelet aggregation in 8 out of 18 dogs, relaxed the bovine coronary artery in 13 of 16 dogs, and lowered systemic arterial blood pressure 5—10 mm Hg in all but 3 animals. These effects of angiotensin II could be blocked by treating the animal with indomethacin (2 mg/kg, i.v.) and mimicked by administration of exogenous prostacyclin. Infusion of the same dose of angiotensin II (10 or 20 ng/kg/min) intravenously did not release prostacyclin; blood pressure increased during intravenous infusion, and platelet aggregation remained unchanged. These data are consistent with the hypothesis that prostacyclin, of renal origin in these experiments, can act as a circulating hormone. Prostacyclin should not be regarded only as an antiaggregatory substance, but also as a potentially important modulator of blood pressure.