Human umbilical vessels are devoid of innervation and therefore endothelial cells may play a fundamental role in the control of feto-placental blood flow. The pharmacological effects of 5-hydroxytryptamine (5-HT), a potent vasoconstrictor agent, in both umbilical arteries and veins from normal term vaginal deliveries were analysed in the present review. It was demonstrated that hypoxia induces the release of an unidentified endothelium-derived contracting prostanoid (EDCP) which acts as an antagonist of the endothelium-derived relaxing factor (EDRF/NO). This prostanoid potentiates the effect of 5-HT in umbilical artery strips. However, all informations should be interpreted cautiously in relation to the contribution of EDRF/NO, hypoxia and EDCP throughout pregnancy because they were obtained in postpartum artery strips, Recently it has been demonstrated that the relaxant effect of histamine, which is mediated by the release of EDRF/NO decrease during gestation. It is concluded that the endothelium may play an autrocrine/paracine modulatory role, by producing and releasing reactive substances in late pregnancy to influence feto-placental blood flow.