The area of vulnerability (AOV) to ventricular fibrillation (VF) induction by high-voltage shocks has been proposed as a measure of vulnerability to VF. Biphasic shocks spanning the T wave and ranging between 50 V and the upper limit of vulnerability (ULV) to VF were delivered before and after terikalant (1 mg/kg) and barium (1.1 mg/kg load followed by 0.05-0.10 mg/kg/min maintenance) or vehicle in dogs. The AOV decreased by 34% and 28% (p < 0.01) after terikalant and barium (n = 8 dogs each), respectively. Mean ULV, defibrillation threshold (DFT), and ventricular vulnerability period (VVP) decreased by 16%, 23%, and 31% (p < 0.01), respectively, after terikalant, and by 25%, 17% (p < 0.01), and 13% (p = 0.08), respectively, after barium. Vehicle (n = 14) did not significantly alter any of these variables. The ULV was correlated with the DFT before and after terikalant (r = 0.78, p < 0.01) and barium (r = 0.83, p < 0.01). Potassium channel blockers of the current reduce the ability to induce VF; this effect may be related to the anti-fibrillatory action of class III anti-arrhythmic drugs and their ability to decrease DFT.