Premenopausal women have a reduced incidence of cardiovascular disease compared to men of a similar age and postmenopausal women: the vascular effects of oestrogen (E₂ ) have been implicated (Farhat et al. 1996). Acute systemic hypoxia induces vasodilatation in skeletal muscle that is partly adenosine mediated acting via an increase in nitric oxide (NO) synthesis (Ray et al. 2002). E₂ is known to facilitate NO-dependent dilatation. In previous experiments on the rat we hypothesised that acute E₂ administration facilitates the vasodilator response to hypoxia via NO. In direct contrast to our hypothesis, acute administration of E₂ in male rats depressed the increase in integrated femoral vascular conductance (Int FVC) evoked by acute systemic hypoxia (Tomlinson et al. 2006). In this study we tested whether this acute effect of E₂ was via its action on the E₂ receptors ERα/ERβ. Experiments were performed on 3 groups of Saffan-anaesthetised (4-8mg.kg.^-1hr^-1 I.V.) male Wistar rats. In Group 1 (n=12; 233±2g: mean±SEM), cardiovascular responses evoked by breathing 12% O₂ for 5min were tested before and 30, 60 and 90min after administration of 17β-oestradiol (E₂ ; 10μg.kg.^-1 I.V.). In Group 2 (n=8; 216±2g), ICI 182,780 (ICI; 5mg.kg.^-1 I.V.) an E₂ receptor antagonist was given 10min before E₂ . Group 3 (n=4; 195±10g) was a time control for Group 2 in which saline replaced E₂ . Arterial blood pressure (ABP) and femoral blood flow (FBF) were recorded and FVC (FBF/ABP) was calculated. In Group 1, systemic hypoxia evoked a fall in ABP (38±3mmHg, p<0.001, Student’s unpaired t-test) and an increase in Int FVC (of +0.96±0.08 CU, p<0.05). Administration of E₂ had no effect on cardiovascular baselines but the hypoxia-induced increase in Int FVC was depressed (to +0.61±0.08*, 0.36±0.06*, 0.40±0.05* CU) at 30, 60 and 90min after E₂ , while and the fall in ABP was reduced (to 19±3*, 15±2*, 16±3*mmHg) respectively (*: p<0.05 ANOVA and Scheffé’s post hoc test). In Group 2, baseline ABP was significantly reduced after ICI and E₂ (from 123±4 to 114±4*, 111±2*, 111±2*mmHg) at 30, 60 and 90min after E₂ respectively, but ICI prevented the effects E₂ on the hypoxic response. In Group 3, ICI alone reduced baseline ABP (from 123±6 to 107±5*, 103±6*, 102±3* mmHg) and reduced the fall in ABP (from 36±7 to 19±6*, 19±4*, 21±4*mmHg), but had no effect on the hypoxia-induced increase in Int FVC. Since ICI reduced baseline ABP and depressed the hypoxia-induced fall in ABP in Group 3 to a similar extent as acute E₂ in Group 1, this suggests that ICI has agonist properties via ERα and/or ERβ. However, comparison of Groups 1 and 2 suggest that in male rats, exogenous E₂ acutely depresses the muscle vasodilatation and fall in ABP evoked by systemic hypoxia by acting through the ERα/ERβ.