Isolated perfused rabbit mesenteric blood vessels selectively metabolized arachidonic acid to prostacyclin (prostaglandin I2). However, the less lipid soluble prostaglandin endoperoxide (PGH2) administered exogenously was not metabolized by vascular prostacyclin synthetase but was partially degraded to prostaglandin E2 (PGE2). Peptide stimulation (e.g., angiotensin II, bradykinin) resulted in formation of both PGI2 and PGE2 from endogenous arachidonic acid. Denuding the blood vessels of their endothelial layer by perfusion with hypotonic fluid did not affect the metabolism of arachidonic acid or the response to peptide stimulation. suggesting that the cyclooxygenase, prostacyclin synthetase, and angiotensin II receptors are present and functional in the subendothelial smooth muscle cells of the vessel walls. In contrast, exogenous PGH2 either escaped completely unmetabolized or was converted to both PGI2 and PGE2 in the presence of vascular injury induced by hypotonic fluid.