Abstract: This study was aimed at providing scientific basis for the medicinal use of Vitex negundo in hypertension. The in-vivo study was conducted on normotensive anesthetized rats while in-vitro studies were conducted on isolated guinea-pig atria and rat aorta preparations by using isometeric transducers coupled with Powerlab Data-aquisiton system. The crude extract of Vitex negundo (Vn.Cr), produced a dose-dependent (10–100 mg/kg-1) fall in the arterial pressure of anaesthetized rats. When tested in rat aortic ring preparations, Vn.Cr inhibited the low K+ (25 mM) with greater potency as compared to high K+ (80 mM)- and phenylephrine (PE, 1 μM)-induced contractions. Further studies on the inhibitory effect of Vn.Cr against low K+ revealed that the preteatment of tissues with tetraethyl ammonium (TEA; 1 mM) shifted the concentration response curves to the right while glibenclamide (Gb; 10 μM) did not show any effect, hence showing the involvement of non-specific type of K+ channels activation in the vasodilatory effect of Vn.Cr. The plant extract also shifted the Ca++ concentration response curves to the right dose-dependently (0.3-1 mg/mL-1), like that caused by verapamil. In isolated guinea-pig atria, Vn.Cr (0.1-10 mg/mL-1) caused inhibition of atrial force and rate of spontaneous contractions, similar to that exhibited by verapamil. These data indicate that Vitex negundo exhibits BP lowering, vasodilator and cardiac suppressant activities, mediated predominently through K+ channel activation combined with Ca++ channel inhibition.