The coronary vascular effect of various divalent cations and of sodium-metavanadate was compared in isolated perfused rat hearts. Their order of activity was as follows (the concentrations (microM) evoking a half-maximum increase of coronary resistance are indicated (in parentheses): Ni2+ (0.03) greater than Co2+ (0.1) greater than Hg2+ (0.16) greater than VO-3 (0.2) greater than Cu2+ (15) greater than Zn (50). Iron (Fe2+) and cadmium (Cd2+) were ineffective. The order of coronary vasoconstrictor potency of these metal ions differs from the order of their other physico-chemical properties indicating that their coronary action cannot be explained as being singly a consequence of ion-membrane interaction. In contrast to Ni2+, the effect of Hg2+ was totally inhibited by phenoxybenzamine (10(-5)M) indicating that coronary vasoconstriction induced by mercury ions is mediated by alpha-receptors. Coronary vasoconstriction induced by sodium-meta-vanadate was resistant to verapamil while removal of external Ca2+ potentiated its effect. These data suggest that in contrast to Ni2+ and Hg2+, vanadate increases coronary resistance by mobilizing intracellular Ca2+ in vascular smooth muscle cells.