The aim of this study was to assess the role of endothelial cells in the modulation of vasocontractile responses to endothelin‐1 (ET‐1) of human placental vasculature. Isolated stem villi small arteries (diameter =170–250 μm) were obtained from healthy parturients who underwent caesarean surgery during the 39th week of pregnancy for cephalo‐pelvic disproportion. Isometric tension was measured in vascular rings mounted in a myograph system and challenged with ET‐1 (10−12 to 10−6m). The vasocontractile response to ET‐1 was significantly (P< 0.0001) increased in endothelial‐denuded (active tension = 1156 ±214 mN mm−1) as compared with endothelial‐preserved vascular rings (active tension = 458 ± 48 mN mm−1). This difference was significantly (P<0.05) but only partly abolished by the NO synthase inhibitor NΩ‐nitro‐L‐arginine (l‐NOARG, 10−4 m). In endothelial‐preserved rings submaximally precontracted with 5‐hydroxytryptamine (10−6 m), ET‐1 (10−12 to 10−9 m) induced dose‐dependent relaxation (maximum relaxation = 70 ±7%) at 10−9 m, which was followed, at higher doses (10−8 to 10−6 m), by a contraction. In contrast, no relaxation was seen in endothelial‐denuded rings. The relaxation in rings with endothelium was significantly (P< 0.001) reduced by l‐NOARG (10−4 m). Moreover, it was totally abolished by combined pretreatment with L‐NOARG (10−4 m) and the sulphonylurea glibenclamide (10−5 m). In conclusion, endothelial cells modulate the vascular responses to ET‐1 through the release of NO and a substance acting on the ATP‐sensitive K+ channel of smooth muscle of stem villi small arteries from healthy parturients.