The aim of the study was to elucidate the mechanism of the contraction produced by hypoxia in human intrapulmonary artery rings. Hypoxia (5 mm Hg) produced a contraction that was greater when the artery rings were precontracted (with endothelin-1) than when recorded under optimal resting force. The contraction was similar in small-diameter (0.38 to 0.68 mm) and in large-diameter (2.2 to 4.5 mm) artery rings under resting force. Removal of the endothelium markedly reduced or abolished the hypoxic contraction in precontracted artery rings (large diameter, 26 ± 9 to −7 ± 4 g cm−2) or under optimal resting force. Hypoxia markedly reduced or abolished the acetylcholine-induced relaxation in precontracted artery rings without affecting relaxation produced by sodium nitroprusside. Flurbiprofen caused a slight contraction itself (large diameter, 10 ± 3 g cm−2) and significantly inhibited the contraction produced by hypoxia both under resting force (8 ± 2 to 2 ± 1 g cm−2) and in precontracted artery rings (18 ± 2 to 1 ± 1 g cm−2). Verapamil had no significant effect on the hypoxic contraction either under resting force or when precontracted. It is concluded that hypoxic contraction of human pulmonary artery rings depends on the presence of endothelium and is partly due to inhibition of a vasodilator cyclooxygenase product.