Abstract.The vascular responses to 17β‐oestradiol were examined in 23 postmenopausal women (59 ± 7 years [mean ± SD]) using a placebo‐controlled double‐blind crossover design. All women received 1 mg 17β‐oestradiol or placebo (P) sublingually on consecutive days in random order. Axial diameters and blood flow rates of the left common femoral arteries were determined before and 60–80 min after application of verum or placebo as well as 10–30 min after 10 mg isosorbide dinitrate (ISDN) with a quantitative duplex ultrasound technique. Oestradiol induced a vasodilation of femoral arteries (+6.4±4.1% of basal,P<0.001 vs. basal and P), the vessel diameter was unchanged with placebo (+0.7 ± 2.1%). The blood flow rate increased significantly after oestradiol application (+30 ± 28%,P<0.05 vs. basal and P), but not after placebo (+11 ±21%). Mean blood pressure and heart rate remained constant with both drugs. Despite its vasodilatory effect, ISDN significantly reduced the arterial blood flow after pretreatment with oestradiol and placebo, probably through cardiac preload reduction. In conclusion, 17β‐oestradiol alters the vascular tone of systemic arteries resulting in a vasodilation and increase of blood flow. We suggest that these direct vascular actions may contribute to the preventive properties of oestrogens on cardiovascular diseases i