1 The effects of selective thromboxane antagonists and a thromboxane synthase inhibitor on the contraction to 9,11-dideoxy-1la,9a-epoxymethano-prostaglandin F2. (U46619) and oxygen in the human umbilical artery (HUA) were examined. The effect of the antagonists on contractions to both 5-hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) were also examined. 2 U46619 (0.3 nM-10uM) contracted the HUA. This contraction was antagonized by two selective thromboxane receptor antagonists EP092 (10 nM-l uM) and GR32191B (10 nM-I uM). The contraction was not affected by the selective thromboxane synthase inhibitor, dazoxiben (10 nM-1 pM).3 When the oxygen tension was increased from 16 mmHg to 120 mmHg, the HUA transiently contracted. Both thromboxane antagonists inhibited this contraction in a concentration-dependent manner with 1,UM almost completely abolishing the response (the oxygen-induced contraction of the control preparation normally increases with a second exposure to 120 mmHg oxygen). 4 In low (16 mmHg) oxygen, responses to both 5-HT and 5-CT were unaffected by both thromboxane receptor antagonists at concentrations qp to 1 UM. In high oxygen (120 mmHg) responses to both 5-HT and 5-CT were biphasic in nature, with an additional initial high sensitivity phase, which was abolished by a cyclo-oxygenase inhibitor. In high oxygen, EP092 and GR32191B blocked this initial phase in a concentration-dependent manner, returning sensitivity to 5-HT and 5-CT to that seen in low oxygen. 5 The thromboxane synthase inhibitor, dazoxiben, at concentrations greater than 10 nm inhibited the contraction to 120 mmHg oxygen and at 1 jUM, dazoxiben almost abolished the response. In low oxygen, the response to 5-HT was unaffected by dazoxiben at concentrations up to 10piM. In high oxygen, the initial phase of the contraction to 5-HT was inhibited by concentrations greater than 10 nm, with no effect on the maximum response. 6 The results show that thromboxane receptor antagonism or blockade of thromboxane synthesis selectively attenuates oxygen-induced contractions and those responses to 5-HT and 5-CT which are dependent on high oxygen for their expression. This suggests that the contractions caused by high oxygen tension, and the enhancement of the contractile effects of low concentrations of 5-HT and 5-CT in the presence of high oxygen tension are mediated by endogenously released thromboxane A2.