The purpose of this study was to investigate the mechanisms behind the increase in blood pressure observed after intravenous administration of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide), a selective κ-opioid receptor agonist, to the ovine foetus. Intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal blood pressure which lasted 15 min. Pretreatment with phentolamine (1.0 mg/kg i.v.) completely blocked the immediate (1-4 min) pressor effect of U50,488H, but not the subsequent increase in blood pressure after 5 min. In contrast, pretreatment with the vasopressin antagonist ([β-mercapto-β-β-cyclopentamethylene-propionyl)-O-Me 2 -Tyr,Arg 8 ]vasopres sin, 0.06 mg/kg) did not affect the immediate pressor effect of U50,488H, but completely blocked the latter increase in blood pressure after 4 min. These data suggest that the immediate increase in blood pressure caused by U50,488H was mediated by sympathetic activation which was then further sustained by a release of vasopressin.