The inhibitory effects of felodipine, nifedipine and verapamil were compared in vascular smooth muscle. In rat aorta, these inhibitors attenuated the high K(+)-induced contraction with a parallel decrease in the cytosolic Ca2+ level ([Ca2+]i). Maximal inhibition was obtained with 10 nM felodipine, 100 nM nifedipine and 10 microM verapamil. The inhibitory effects were antagonized by an increase in external Ca2+ concentration to 6.5 mM and the addition of a Ca2+ channel activator, 100 nM Bay k 8644. These inhibitors also attenuated the contraction induced by norepinephrine although these effects were weaker than those on high K(+)-induced contraction. Furthermore, these inhibitors attenuated the norepinephrine-stimulated [Ca2+]i more strongly than contraction. In contrast, none of these inhibitors inhibited the transient increase in [Ca2+]i and muscle tension induced by norepinephrine in Ca(2+)-free solution and the Ca(2+)-induced contraction in permeabilized smooth muscle. These results suggest that felodipine, nifedipine and verapamil inhibit smooth muscle contraction by inhibiting Ca2+ channels at concentrations which do not change Ca2+ release or Ca2+ sensitivity of contractile elements.