Previous studies on isolated blood vessels indicate that (1) withdrawal of magnesium ([Mg2+]0) induces calcium-dependent contractile responses, and (2) Mg2+]0 and verapamil (VE) inhibit calcium influx across the cell membrane. The present study, using isolated rat aortic strips and portal veins, was designed to assess the interactions of [Mg2+]0 and VE on increases in active tension and contractility induced by withdrawal of [Mg2+]0.[Mg2+]0 was found to: (1) enhance VE-induced inhibition of portal vein amplitude, and (2) antagonize VE-induced enhanced frequency of spontaneous phasic contractions in portal veins. Both [Mg2+]0 and VE could prevent and reverse the increases in active tension developed in aortic smooth muscle upon removal of [Mg2+]0.[Mg2+]0 markedly potentiated the inhibitory effect of verapamil on calcium-induced contractions of K+-depolarized aorta but not in K+-depolarized portal vein. This synergistic effect in aortal could be due to the influence of Mg and VE at the membrane and/or the influence of Mg at intracellular sites resulting in decreased levels of functional (activator) cytoplasmic Ca2+. On the other hand, the lack of synergism in portal vein could indicate that both of these agents might be inactivating the same membrane channels involved in calcium influx.