8-iso-PGE2, an E2-isoprostane, decreased GFR and RPF dose-dependently in rats, but with lesser potency than 8-epi-PGF2α, an F2-isoprostane. This effect was abolished by SQ29,548. 8-iso-PGE2 displaced [3H]SQ29,548 or [125I]BOP binding in aortic smooth muscle cells with the affinity rank order of SQ29,548 > = I-BOP > U46,619 > 8-iso-PGE2 > PGF2α, while it activated phospholipase C with a potency greater than those of I-BOP or U46,619 and lesser than that of 8-epi-PGF2α. We concluded that 8-iso-PGE2 is a renal vasoconstrictor linked to phosphoinositide metabolism. Its vascular smooth muscle contractile actions are likely mediated through activation of putative thromboxane A2 receptor-like “isoprostane receptors”. © 1993 Academic Press, Inc.