Urotensin II (U-II) is a highly conserved cyclic peptide that binds to its cognate G protein coupled receptor U2R. The U-II-U2R system is the most potent vasconstrictor known. Pre-eclampsia is characterised by hypertension and high levels of protein in the urine, with the disease manifesting in approximately 5-7% of pregnancies. Here we investigate the roles of U-II and U2R in the physiology of the normal and pre-eclamptic placentae, in particular, focusing in on placental arteries and the syncytiotrophoblast (the cellular interface between the mother and the fetus). We defined pre-eclampsia for this study as a BP >140/100 on two separate occasions with >2+ proteinuria on dipstick. All patients were >37 weeks gestation. Changes in the levels of U-II ligand or receptor would be expected to alter the physiology of the placenta and possibly mediate the hypertensive response characteristic of pre-eclampsia. Previous studies have suggested an increased level of U-II in pre-eclamptic patients although nothing was known about the receptor (Balat et al. 2005). Here we present immunolocalisation studies that indicate the U2R is within the syncytiotrophoblast and fetal arterial vessels of normopregnant and those with pre-eclampsia. Addition of U-II to the BeWo cell line (a recognised syncytiotrophoblast model) led to activation of extracellular signal-regulated kinase 1/2 (ERK). Furthermore contractions of normal placental arteries were measured using wire myographic studies and showed U-II has an EC₅₀ of 600±5nM (n=4). Contractile responses of vessels to U-II from pre-eclamptic placentas are to be investigated. Real time PCR studies showed a 1.8-fold increased level (although not significant using two-way Mann Whitney U test) of U2R in patients with pre-eclampsia compared to patients without pre-eclampsia (n=7 for each). We, however, failed to detect U-II mRNA in the placenta suggesting the peptide is synthesised remotely. We have identified the presence of the U-II receptor in human placenta localised to the syncytiotrophoblast and placental vessels. Administration of U-II peptide vasoconstricted isolated placental vessels, consistent with the known role of U-II in the vasculature. UII stimulation of the human placental BeWo cell activates ERK signalling. Ascribing a function to this will provide a valuable insight into the role of U-II in this tissue and may provide further insights into the pathogenesis of pre-eclampsia.