The acute cellular electrophysiologic actions of amiodarone on isolated neonatal and adult canine ventricular muscle and Purkinje fibers were evaluated using standard microelectrode techniques. Amiodarone, 10(-6) to 5 X 10(-5) M (0.68 to 34 micrograms/ml), significantly (p less than 0.05) prolonged adult ventricular muscle action potential duration and voltage-dependent refractoriness at all concentrations, thereby demonstrating typical class III antiarrhythmic effects. Similar concentrations had no significant effects on neonatal ventricular muscle. Amiodarone significantly shortened action potential duration and refractoriness of both neonatal and adult Purkinje fibers, with neonatal fibers having a greater sensitivity to the drug. At the standard stimulation rate of 1 Hz, amiodarone had no effects on action potential amplitude or maximal rate of rise of phase 0 of the action potential (Vmax) of any tissues. At faster stimulation frequencies (2 to 4 Hz), amiodarone produced frequency-dependent decreases in action potential amplitude and Vmax of all neonatal and adult preparations. The data indicate that amiodarone exhibits a complex aggregate of electrophysiologic actions that include significant frequency-related class I effects. Compared with adult myocardium, neonatal tissues demonstrated altered responsiveness to amiodarone, a feature common to many antiarrhythmic compounds.