1. The aim of the present study was to investigate the mechanism underlying biochanin A-induced relaxation of the aorta in spontaneously hypertensive rats (SHR). 2. The tension in isolated ring preparations of thoracic aortas from normotensive (Wistar-Kyoto (WKY) rats) and SHR at 5 and 10 weeks of age was measured isometrically. 3. Biochanin A (10(-7) to 10(-4) mol/L) induced a concentration-dependent relaxation in aortic rings from both strains at the age of 5 and 10 weeks and the relaxation was greater in rings from 10-week-old SHR compared with age-matched WKY rats. The vasorelaxation induced by biochanin A was significantly reduced by denudation of the endothelium in aortic rings from SHR, but not WKY rats. Treatment with either indomethacin, a cyclo-oxygenase inhibitor, or N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, had little effect on the relaxation induced by biochanin A in aortic rings from either strain. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly attenuated the relaxation induced by biochanin A in aortic rings from both strains, although the extent of reduction was greater in WKY rats than SHR. Conversely, treatment with 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, or tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the vasorelaxation induced by biochanin A in rings from SHR but not WKY rats. 4. The greater vasorelaxation produced by biochanin A in aortic rings from 10-week-old SHR is endothelium dependent. Different mechanisms underlie the relaxant effects of biochanin A in aorta from SHR and WKY rats. The mechanisms of biochanin A-induced vasorelaxation in thoracic aortas from both normotensive and hypertensive rats involve ATP-sensitive potassium channels and, in addition, in rings from the hypertensive strain at 10 weeks of age, an endothelium-derived activation of smooth muscle cell potassium channels contributes to the vasorelaxation observed.