1 Reactivity of goat isolated pulmonary arteries and veins to a variety of vasoactive agents was investigated. 2 Bradykinin (Bk), acetylcholine (ACh), noradrenaline (NA), prostaglandin A1 (PGA1), PGE2, PGF2 alpha and histamine induced dose-dependent contractile responses on veins; 5-hydroxytryptamine (5-HT) induced veno-relaxation. Angiotensin was virtually inactive. 3 Angiotensin, NA, Bk, histamine and 5-HT produced concentration-dependent contractile responses on the arterial strips; these arteries failed to respond to ACh, PGA1, PGE2 or PGF2 alpha. 4 The pulmonary veno-relaxant response to 5-HT was found to be resistant to propranolol, indomethacin, metiamide, cimetidine, methysergide, atropine and morphine. These findings appear to exclude the involvement of adrenergic mechanisms and prostaglandin generation as well as activation of classical M and D-tryptamine receptors by 5-HT in the goat pulmonary veins. This response may be mediated via a presynaptic inhibitory 5-HT receptor. 5 5-HT-induced arterial contractile responses were antagonized by methysergide, showing the occurrence of classical D receptors in the goat pulmonary artery. 6 It is concluded that differential reactivity of pulmonary arteries and veins to vasoactive agents may play differential role(s) in the pathophysiology of pulmonary disease. 5-HT may exert an antiinflammatory activity in goat pulmonary veins.