Various complications of pregnancy such as preeclampsia, diabetes and other causes of uteroplacental insufficiency are associated with peroxidation in placenta. Peroxides exert significant placental vasoconstriction; but the mechanisms responsible for their action is not known. Nonenzymatic oxidation of the ubiquitous arachidonic acid leads to formation of stable prostanoids termed isoprostanes. We investigated the mode of action of 8-iso-PGF2αand 8-iso-PGE2 (abundantly produced) on human term placental and umbilical arteries and veins, and postulated that they may in part reproduce effects of peroxides. Rings of vessels were set up in tissue baths under optimal passive tension. Both 8-iso-PGF2αand 8-iso-PGE2 caused strong constriction of all 4 vessel types equivalent to that of KCl; EC50 of 8-iso-PGE2 was 0.1 μM and that of 8-iso-PGF2α1 μM. The effects of both isoprostanes were unaffected by inhibition of phospholipase A2, cyclooxygenase or thromboxane synthase. However, the selective thromboxane receptor blocker L670596 competitively antagonized effects of the isoprostanes. pA2 values of L670596 for isoprostanes and the thromboxane mimetic U46619 did not differ, albeit interaction of isoprostanes with receptors distinct from that of thromboxane can not be excluded. Further characterization of 8-iso-PGF2αand 8-iso-PGE2 action revealed dependence of extracellular calcium via L-type calcium channels; constriction was annulled by abscence of calcium, addition of EGTA, as well as by nifedipine but not by a receptor-operated channel blocker SK&F96365. Results indicate that isoprostanes cause constriction of placental and umbilical vessels by a mechanism apparently dependent of thromboxane receptors and voltage-operated L-type calcium channels. We speculate that inhibition of effects of isoprostanes may be beneficial in placental insufficiency.