Summary—As feto‐placental vessels in humans are not innervated, regulation of vascular tone in the fetal extracorporeal circulation most likely depends on either circulating hormones or local paracrine mechanisms. However, the latter have not yet been fully investigated. The aim of our study was to characterize vasomotor behaviour of resistance stem villi arteries when challenged with various constrictor and dilator agents, with special emphasis on the physiological importance of endothelium. The latter is poorly characterized in this particular vascular bed in humans. Villous stem arterial rings (internal diameter 182 ± 6 μm) were isolated under microscopy from term human placentae obtained after cesarean section. The vessels were mounted as ring preparations in an isometric myograph for tension measurements. Endothelium was removed from some of the rings by gentle insertion of a knotted human hair into the vascular lumen. Of the three vasoconstrictors tested, endothelin‐1 (ET‐1) showed the greatest potency, being 1,000 times more potent than serotonin and phenylephrine. The classical endothelium‐dependent vasodilators, acetylcholine, adenosine diphosphate (ADP) and histamine, caused dose‐dependent relaxation of the rings; an effect which was completely abolished by the removal of endothelium. Pre‐treatment with the nitric oxide (NO) synthase inhibitor, Nω‐nitro‐L‐arginine, also markedly reduced the endotheliumdependent relaxant responses to ADP. By contrast, the vasodilatory response to sodium nitroprusside was not affected by endothelial removal. We conclude that i) ET‐1 is a potent vasoconstrictor of the human placental vascular bed and ii) placental villous endothelial cells synthesize and release relaxing factor(s) wh