Angiotensin II (All) can release arachidonic acid metabolites such as prostacyclin (PGI₂) and PGE2 from cells in cultures. It has recently been reported that the AT₁ selective nonpeptide All receptor antagonist losartan had similar effects. The present study was undertaken to further evaluate the effects of All and losartan on cells which synthesize prostaglandins, including vascular smooth muscle, endothelial, and glial cells. Inhibition of specific [¹²⁵I]AII binding was demonstrated in porcine smooth muscle cell (PSMC) suspensions with unlabeled All and losartan^ The IC₅₀ values were 1.3 × 10^-9 mol/L and 7.7 × 10⁹ mol/L, respectively. PD123177 (an AT2 selective antagonist) had no effect on binding. All produced a concentration- related increase in calcium mobilization (fura-2 fluorescence) which was blocked by losartan (ICso = 8.4 × 10^-8 mol/L) but not by PD123177 (1(T6 mol/L). All (10⁷ to 10⁵ mol/L) stimulated the basal release of PGI2 by 100%. This response was blocked by losartan (10^-6 to 10^-5 mol/L) but not by PD123177 (10^-7 to 10^-5 mol/L) and neither agent stimulated basal release in PSMC. Similar effects of All and antagonists were observed upon receptor binding and PGE₂ release in primary rat astrocyte (RA) cultures. All did not release PGI₂ from porcine endothelial cells, bovine pulmonary arterial endothelial cells, or rat C6 glioma cells. Losartan had no significant effect at 10^-5 mol/L. By contrast, bradykinin or the calcium ionophore A23187 dramatically increased PGI2 release in each of these cells. All did not release either PGI₂ or thromboxane A₂ from rat spleen macrophages which were responsive to A23187. Losartan and PD123177 had no effect at 10^-5 mol/L. It is concluded that All release of prostacyclin is cell type specific. The All-induced PGI₂ and PGE₂ release in PSMC and RA, respectively, is AT₁ receptor subtype mediated. Losartan had no effect on the release of arachidonic acid metabolites. Am J Hypertens 1992;5:648-656.