1 We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent contraction (EDC) in the rabbit isolated intrapulmonary artery.2 Removal of the endothelium almost abolished the contraction induced by SP (10' M) while it did not attenuate the contraction induced by SP (lI-V M), NKA (0 -l10-7 M) or NKB (10' and 10 M). 3 The EDC induced by SP (10' M) was abolished by NKI antagonists (FK-888, and SR-140333) but not by an NK2 antagonist (SR-48968). 4 The EDC induced by SP was attenuated by cyclo-oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5 The rank order of potency causing endothelium-independent contraction (EIC) was NKA > NKB> SP. The EIC induced by SP (1O' M) was attenuated by an NK2 antagonist but not by NK, antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase inhibitors or a TXA2 antagonist. 6 In conclusion, SP at 101 M induces EDC via endothelial NK, receptors and TXA2 production, and SP at 10-7 M induces EIC via NK2 receptors in the rabbit intrapulmonary artery.