The effect of amiodarone was investigated in a canine model of myocardial infarction. The left anterior descending coronary artery was occluded in 24 anesthetized dogs. After 15 minutes of coronary artery occlusion, the ischemic myocardium at risk of necrosis was determined by labeling the heart with technetium-99m-labeled human albumin microspheres injected into the systemic circulation through the left atrium, and the dogs were than randomized to either a saline-treated control group (n = 13) or an amiodarone-treated group (n = 11) that received i.v. amiodarone, 10 mg/kg, administered in a single bolus 30 minutes after coronary artery occlusion. Myocardial infarct size was determined directly after 6 hours of coronary occlusion by incubation of sections of myocardium in triphenyltetrazolium chloride, a dehydrogenase stain, and expressed as a percentage of left ventricle below occlusion. Autoradiography of the stained myocardial sections was performed to determine the ischemic myocardium at risk of necrosis, which was similar in the control and amiodarone-treated groups (31.8 +/- 2.8% vs 32.5 +/- 3.3% of the left ventricle, respectively). In the amiodarone-treated group, only 67.1 +/- 8.4% of the myocardium at risk became necrotic; in the control group, 97.5 +/- 7.7% of the myocardium at risk became necrotic (p less than 0.01), representing 21.8 +/- 3.5% vs 31.1 +/- 2.8% of the left ventricle below occlusion, respectively (p less than 0.025). Amiodarone decreased heart rate, contractility and afterload. Its beneficial action on infarct size is related presumably to reduced myocardial oxygen demand.