Fresh rings of arteries and veins obtained from surgical specimens generated an unstable substance, prostacyclin (prostaglandinx, [P.G.X]) WHICH IS A POTENT INHIBITOR OF PLATELET AGGREGATION. The spontaneous generation of prostacyclin as well as its generation from exogenous arachidonic acid was inhibit by incubation of the tissues with a prostaglandin-synthetase inhibitor such as indomethacin, whilst the generation induced by prostaglandin endoperoxides was not. 15-Hydroperoxyarachidonic acid (a lipid hydroperoxide) inhibited the generation of prostacyclin in all three situations. It is postulated that prostacyclin is important for prevention of deposition of platelets on the vessel wall and that the inhibition or prevention of the generation of prostacyclin is important in the genesis of diseases, especially those in which increased lipid peroxidation occurs, such as atherosclerosis.