An acute vasodilatory action of 17-β oestradiol in many vascular beds depends upon oestrogen receptor (ERα and ERβ) activation. The role of 17-β-oestradiol in regulating human vascular tone is of interest in many physiological settings including the uteroplacental unit. Maternal serum levels of 17-β oestradiol, and uterine blood flow, increase during pregnancy and 17-β oestradiol acutely relaxes uterine arteries in vitro. Alternatively, little is known of 17-β oestradiol influences on placental vascular tone. As the placenta lacks autonomic regulation, arterial tone is controlled by locally derived substances one of which may be oestrogen. The placenta also offers a source of non-pathophysiological blood vessel specimens, and it was therefore pertinent to investigate if 17-β oestradiol and agonists of ERα or ERβ, have a role in the regulation of placental arterial tone. Chorionic plate arteries (200-500µm) were dissected from placentas collected (n=12, with LREC approval) from normal term pregnancies. Vessels were bathed in Physiological Salt Solution (PSS, 5%CO₂/95%air, 37^oC) and isometrically constricted with the thromboxane receptor ligand U46619 (1µM). Upon stable constriction, incremental doses (0.05-30μM) of 17-β oestradiol, 17-α oestradiol (a putatively inactive stereo-isomer), ERα agonist propylpyrazoletriyl (PPT) or ERβ agonist diarylpropionitrile (DPN) were applied. Vessels were washed with PSS, re-constricted with U46619 and exposed to a single dose (30µM) of 17-β oestradiol, 17-α oestradiol, PPT or DPN. In a subset of experiments, the influence of 17-β oestradiol, 17-α oestradiol, PPT or DPN on U46619-induced Ca²⁺-sensitisation (pCa 6.7) of α-toxin permeabilised arteries was studied. Pre-constricted arteries (n=6) significantly relaxed in response 17-β oestradiol from 1µM-30µM (p<0.001, 2 way anova of Arcsine transformed data, bonferroni post hoc test) and to DPN from 2µM-30µM (Figure 1). Similar relaxations to PPT or 17-α oestradiol were not evident. Separate single dose 30µM exposure to 17-β oestradiol (n=6) or DPN also relaxed pre-constricted arteries, to 41.8±1.1% or 50.5±3.9% respectively (P<0.01, one way anova) of U46619 max-constriction. In permeabilised arteries (n=5), none of the agents significantly relaxed U46619-induced tone at pCa 6.7. In summary, the acute relaxation of human placental vascular tone by 17-β oestradiol may, in part, be due to signalling via ER-β but does not appear to involve direct activation on smooth muscle of Ca²⁺-desensitisating pathways. It remains to be seen if similar actions are evident in other human arterial vascular beds but nonetheless places oestradiol as a potential endocrine regulator of human placental vascular tone.