The effects of extracellular Ca and Ca antagonists on vanadate-induced contractions of vascular smooth muscles of aortae and mesenteric arteries from rabbits, guinea pigs, and Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were studied. Vanadate-induced contractions of aortae were greatly diminished by extracellular Ca removal; the size of the remaining contraction was variable. Vanadate-induced contractions of mesenteric arteries, which were only observed in the presence of elevated K, were suppressed by the removal of Ca. Verapamil and nifedipine depressed vanadate-induced contractions of aortae from WKY and SHRSP, whereas they produced no or only slight inhibition of responses in guinea pig and rabbit aortae. Ca uptake into smooth muscle cell increased in the presence of vanadate, but the increase was much less than that induced by high K. In saponin-skinned smooth muscle, vanadate depressed the Ca-induced contraction. It is concluded that the vanadate-induced contraction utilizes both extracellular and intracellularly bound Ca, the relative contribution of which varies from preparation to preparation.