We compared the acute electrophysiological effects of amiodarone (AM) and tetrodotoxin (TTX) on action potentials of isolated canine Purkinje fibers. All two drugs suppressed action potential amplitude, overshoot, and maximum rate of upstroke of action potential, and shortened action potential duration (APD). 2. However, higher concentrations (4.4 x 10(-4) M) of AM showed differential effects on APD, compared with TTX. 3. These differences between effects of AM and TTX suggest that in case of high concentration of AM the APD-shortening by AM might be masked by AM's other action(s), while in low concentration the APD-shortening effect of AM, probably due to decrease in Na+ and slow Ca2+ current, was predominant.