The early use of atropine in the management of sinus bradycardia, with associated hypotension, spurred a continuing controversy that has found only partial solution in animal models. Experimentally there is increased sensory and autonomic motor activity with acute coronary occlusion. For example, in the cat, increased cholinergic activity was evidenced by the absence of bradycardia with atropinization and vagotomy, although these pretreatments accelerated the onset of significant ventricular arrhythmias. Atropine in experimentally infarcted dogs increased ischemia, while elevated heart rates reduced the threshold for ventricular fibrillation (VF) and vagal stimulation increased the threshold for VE largely independent of heart rate. Specific clinical studies failed to support much of the animal data, although reports of tachyarrhythmias and VF resulting from the administration of atropine extended the controversy. The animal models, in the main, failed to mimic the clinical situation, for: 1) pentobarbital, with its propensity to alter some autonomic reflexes, dominated earlier work; 2) relatively large doses of atropine were employed; 3) the animals were presumed to be free of coronary and cardiac disease, factors known to influence autonomic reflexes; and 4) vagotomy and atropinization commonly preceded the acute occlusion.