Vasoactive intestinal peptide (VIP) is one of the chief neurotransmitters of nonadrenergic noncholinergic nerve fibers. In this study, we investigated the effect of VIP on the pulmonary circulation in isolated perfused rat lungs. Baseline pressures of the pulmonary artery for the isolated rat lungs were not affected by 3 × 10^-8.M IP. VIP caused dose-dependent pulmonary vasodilation when the pulmonary vascular bed was constricted with 20 mM KCl. This vasodilative effect of VIP was inhibited by 1 × 10^-6M L-N^ω-nitro-arginine, an endothelium-derived relaxing factor (nitric oxide) inhibitor, and was restored by the addition of 10^-4ML-arginine, a substrate of nitric oxide. VIP also caused suppression of the ANGII pressor response, and this VIP-induced suppressive effect was reduced when L-N^ω-nitro-arginine or 3 × 10^-6M meclofenamate was added to the perfusate. These results indicate that VIP causes pulmonary vasodilation in isolated rat lung and suggest the possible involvement of NO and/or cyclooxygenase metabolites in VIP-induced pulmonary vasodilation.