Amiodarone is a benzofuran derivative with depressant effects on all electrically active cardiac tissues and important antiarrhythmic properties after long-term dosing. We evaluated its short-term effects on myocardial repolarization and refractoriness in eight patients. The duration of repolarization was evaluated by a new method, the paced evoked-response system, which records the dominantly local repolarization that follows a controlled (paced) depolarization from the same site. Intravenous amiodarone (5 mg/kg) prolonged the latency of the stimulus peak-evoked T wave interval an average of 39.4 msec (+15% of control) 10 min after infusion. In animal experiments these changes correlated well with simultaneous increases in the paced monophasic action potentials obtained with suction electrode catheters. There was also a lengthening of the effective refractory period of the atrioventricular node from 270 +/- 20 to 295 +/- 25 msec. Atrial and ventricular refractoriness were not altered. Amiodarone early activity at the atrial and ventricular level apparently differs from that long-term therapy and appears to favor changes in action potential duration and not changes in refractoriness.