We studied the putative relaxant effects of several isoprostanes (8-iso-PGE1, and 8-iso-PGE2, 8-iso-PGF1alpha, 8-iso-PGF1beta, 8-iso-PGF2alpha, and 8-iso-PGF2beta) on pulmonary (PA), mesenteric (MA), coronary (CA) arteries and pulmonary veins (PV), from newborn and 2-week-old piglets. Isoprostanes were compared with agonists of the EP (PGE1, PGE2, and misoprostol), DP (PGD2), and IP (iloprost) receptors. Isoprostane-induced relaxation was only observed when TP receptors were occupied (by U46619) or blocked (by SQ 29,548). Under these conditions, 8-iso-PGE2 induced a relaxation of PA (but not PV or MA) that increased with postnatal age. 8-iso-PGE1, 8-iso-PGE2, and 8-iso-PGF2alpha evoked modest relaxations in CA. 8-iso-PGE2-induced relaxation of PA was impaired by endothelium removal and by the presence of blockers of NO synthase (L-NAME), guanylate cyclase (ODQ), or EP receptor (AH6809). PGE1, PGE2, and misoprostol (but not PGD2 or iloprost) induced a relaxation of PA that increased with age. In conclusion, occupancy or blockade of TP receptors unmasked a relaxant effect of 8-iso-PGE2 in piglet PA. This relaxation increased with postnatal age, was endothelium-dependent and involved EP receptors and NO.