Studies have recently demonstrated that long-term oestrogen therapy improves endothelium-dependent and endothelium-independent vasodilatation in the conductance vessels of biological males. We sought to determine if an acute single dose of oestrogen might similarly improve vasodilator function in young males. In a randomized, double-blind, placebo-controlled, crossover study, we compared the effects of 1 mg of sublingual 17beta-oestradiol (E(2)) and placebo on endothelium-dependent and endothelium-independent vasodilatation in the brachial artery using a non-invasive ultrasound technique. We recruited 30 young males based on a power calculation. Neither acute sublingual oestrogen nor placebo affected flow-mediated vasodilatation [5.32+/-0.78% and 5.28+/-0.60% respectively (mean+/-S.E.M.), P=0.94]. Responses to nitroglycerine were similar after oestrogen or placebo (16.01+/-0.86% and 15.29+/-1. 19%, P=0.47). Basal blood flow and flow during reactive hyperaemia did not differ after oestrogen or placebo. Heart rate and blood pressure were similar during both treatment phases of the study. The absolute change in serum oestradiol levels was greater after the oestrogen treatment phase than after placebo (1509+/-87 versus -13+/-4 pmol/l, P<0.0001). Despite achieving supra-physiological oestradiol levels, the acute administration of sublingual E(2) does not appear to improve endothelium-dependent or endothelium-independent vasodilatation, at least acutely, in the brachial artery of young males. In keeping with our previous study, these data suggest that a period of oestrogen 'priming' (possibly to induce receptor-mediated nitric oxide synthesis) may be required to yield an improvement in vascular function in males.