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 synthesis (NO; Ray & Marshall, 2002). E₂ can facilitate NO synthesis (Chen et al. 1999), thus, we hypothesised that E₂ may facilitate hypoxia-induced muscle vasodilatation. Experiments were performed on anaesthetised (Saffan; 4-8mg kg^-1 h^-1 i.v.) age-matched male (n=12; 233g±2g) and female Wistar rats, the latter being divided into low E₂ (n=9; 163±4g) and high E₂ (n=5; 184±11g) groups: oestrous cycle stage was determined by vaginal smears. The response evoked by breathing 12% O₂ for 5min was tested before and 30, 60 and 90min after administration of 17β-oestradiol (10μg kg^-1 i.v.). Arterial blood pressure (ABP) and femoral blood flow (FBF) were recorded and femoral vascular conductance (FVC=FBF/ABP) was calculated. Results are expressed as mean ± S.E.M. In male rats, systemic hypoxia evoked a fall in ABP (30±4mmHg, P<0.001) and an increase in integrated FVC (of 1.03±0.1 CU, P<0.05). After administration of E₂ the hypoxia-induced increase in integrated FVC was depressed (0.67±0.08, 0.41±0.06, 0.44±0.05 CU at 30, 60 and 90min after E₂ respectively: P<0.01 ANOVA and Dunnets post hoc test). In low E₂ females, hypoxia evoked a similar increase in integrated FVC (1.03±0.3 CU) to that of males, and after E₂ administration, hypoxia-induced increases in integrated FVC were also depressed (to 0.59±0.2, 0.4±0.09, 0.4±0.12 CU, P<0.05). However, hypoxia-induced increase in integrated FVC in high E₂ females was only 50-60% relative to males before E₂ administration (0.56±0.12 CU) and no further depression after acute administration of E₂. These results contrast with our hypothesis. They suggest that in female rats, when endogenous E₂ is high, hypoxia-induced muscle vasodilatation is already depressed. A similar depression can be induced in males and low E₂ females by administration of exogenous E₂. We therefore propose that E₂ affects the balance of vasoconstrictor and vasodilator influences that are exerted upon muscle vasculature in hypoxia. E₂ may decrease the vasodilator component, which is mediated by adenosine and NO and/or facilitate the vasoconstrictor component, which is mediated by sympathetic activity and vasoconstrictor hormones.