1. In rat isolated aorta the class Ic antiarrhythmic drug, propafenone, dose-dependently inhibited the contractile responses induced by high K (80 mM) and noradrenaline (NA, 10(-5) M), the IC50s being 2.5 +/- 0.7 x 10(-6) M and 8.7 +/- 0.8 x 10(-6) M, respectively. These inhibitory actions were also observed with propafenone added after the induced contractions. 2. Contractile responses induced by addition of Ca to 0 Ca high-K solution were also inhibited by propafenone (IC50 = 2.5 +/- 0.8 x 10(-6) M). Moreover, propafenone inhibited the contractile responses elicited by NA in strips incubated in 0 Ca (IC50 = 1.9 +/- 0.9 x 10(-6) M). 3. Propafenone also inhibited (IC50 = 1.2 +/- 0.4 x 10(-5) M) the development of spontaneous mechanical activity in portal vein segments. 4. Propafenone, 5 x 10(-6) M and 10(-5) M, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting strips. 5. These results indicated that in rat isolated aortae and portal veins propafenone inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores. As a consequence it would reduce the concentration of intracellular free Ca available at the contractile apparatus for vascular smooth muscle contraction.