1. The inhibitory effects of flecainide were studied on contractile responses in rat isolated aortae and caudal artery and on spontaneous mechanical activity in portal vein segments. 2. In rat isolated aorta flecainide, 10(-6) M-5 x 10(-4) M, inhibited in a dose-dependent manner the contractile responses induced by high K (80 mM) and noradrenaline (NA, 10(-5) M). These inhibitory actions were observed when flecainide was added before or after the induced contractions and were similar in aortae with or without endothelium. 3. Contractile responses induced by addition of Ca to Ca-free high-K solution were also dose-dependently inhibited by flecainide (IC50 = 2.5 +/- 0.3 x 10(-5) M). Moreover, flecainide inhibited the contractile responses elicited by NA in rings incubated in Ca-free solution. 4. Flecainide also inhibited the spontaneous mechanical activity in portal vein segments (IC50 = 6.5 +/- 0.9 x 10(-5) M). 5. Flecainide, 10(-4) M, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting aortae. 6. These results indicated that in rat isolated aortae, caudal arteries and portal veins, flecainide inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores, thus decreasing the availability of intracellular free Ca required for vascular smooth muscle contraction.