1 Vasodepressor effects of prostacyclin (5z-5, 6-didehydro-9-deoxy-6, 9alpha-epoxyprostaglandin F1) and its decomposition product 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha) have been compared with those of prostaglandin E2 (PGE2) in anaesthetized rats and rabbits. 2 In rats intravenous prostacyclin produced hypotension and was 4--8 times more potent than PGE2 and about 128 times more potent than 6-oxo-PGF1alpha. 3 In rabbits also, intravenous prostacyclin (less than 2 microgram/kg) produced hypotension and was twice as active as PGE2 and approximately 250 times more active than 6-oxo-PGF1alpha. 4 In rats and rabbits vasodepressor responses induced by prostacyclin were similar in magnitude after either intravenous or intra-aortic administration. 5 Thus, in both species prostacyclin resembles PGE2 in producing vasodepression but does not lose activity on passage through the lungs. The results emphasize the need to consider prostacyclin in addition to PGE2 as a major determinant influencing blood pressure.