As premenopausal women have a lower incidence of cardiovascular disease than age-matched males or postmenopausal women, ovarian hormones have been thought to exert a vascular protective effect. Hormone replacement therapy (HRT) may confer similar risk reduction in postmenopausal women (Austin, 2000). However, this remains controversial with a recent study reporting increased adverse vascular events in postmenopausal women prescribed combined HRT (The Writing Group for WHI Investigators, 2002). If the positive or negative health effects of HRT are related to oestrogen receptor (ER) subtype-specific actions, it may be beneficial to utilise ER subtype-specific agonists in future HRT therapy. Thus we examined the effects of two such compounds, 4,4Ô,4ÔÔ-(4propyl-[¹H]-pyrazole-1,3,5triyl)tris-phenol (PPT) and 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), putative agonists of ER-α and ER-β, respectively (Tocris Cookson Ltd, UK), on vascular contractility and compared these with previously described endothelial-independent relaxant actions of acute 17β-oestradiol application (Shaw et al. 2000). Mesenteric resistance arteries (262-417 µm diameter), were isolated from male Wistar rats (n = 16) humanely killed by stunning followed by cervical dislocation in accordance with national guidelines and mounted on a wire myograph in HCO₃^–-buffered physiological saline solution (37 °C, 95 % air and 5 % CO₂). Vessels were preconstricted with high K⁺ solution (60 mM), and exposed to cumulative concentrations of 17β-oestradiol, PPT or DPN (1 nM-30 µM). PPT induced relaxation of preconstricted arteries in the concentration range 0.3-30 µM. The magnitude of vasodilatation to PPT was larger than for 17β-oestradiol across this range (ANOVA, P = 0.002). Alternatively, the magnitude of relaxation to DPN was significantly less than to 17β-oestradiol across similar concentrations (P < 0.002). Maximal relaxations (30 µM) were 101 ± 0.52 % (mean ± S.D.), 117 ± 0.37 % and 41 ± 0.29 % for 17β-oestradiol, PPT and DPN, respectively. Thus this pilot study demonstrates that acute relaxation of preconstricted mesenteric arteries with ER agonists or 17β-oestradiol occurs with the relative potency of PPT > 17β-oestradiol > DPN.