1. The vasorelaxant effects of seven NA+ channel blockers (i.e., class I antiarrhythmic agents), quinidine, disopyramide, imipramine, lidocaine, mexiletine, flecainide, and desipramine, were investigated in isolated endothelium-denuded rat aorta. 2. All drugs induced a concentration-dependent relaxation in aorta precontracted with either 80 mM KCl or 10(-5) M noradrenaline and, with the exception of mexiletine, they were more potent in inhibiting KCl-induced contractions. 3. The degree of inhibition of high KCl-induced contractions produced by quinidine and desipramine increased with the time of depolarization. Furthermore, the inhibitory effect of quinidine also increased in aorta preincubated in 40 mM KCl, whereas the inhibitory effects of other antiarrhythmics were almost similar in 5 or 40 mM KCl solution. 4. In conclusion, all these class I antiarrhythmic drugs inhibited Ca2+ entry through voltage- and receptor-gated channels as well as Ca2+ release from intracellular stores. As a consequence, they decrease the availability of intracellular free Ca2+ required for vascular smooth muscle contraction.