Calcium antagonists are able to reduce the incidence of early ischemic arrhythmias when given as pretreatment in a variety of models of acute myocardial regional ischemia. Two possible modes of action are electrophysiologic and anti-ischemic. First, a direct electrophysiologic effect of the calcium antagonist agents on the inward calcium current could inhibit four calcium-dependent phenomena, each of which has been linked to the development of ischemic arrhythmias: the slow response, delayed afterdepolarizations (DADs) and calcium-dependent automaticity, enhanced membrane depolarization and conduction slowing. The special circumstances in which each of these could occur are delineated. An anti-ischemic effect of calcium antagonists must also be considered in some models, because of the negative inotropic, negative chronotropic and coronary and peripheral vasodilator properties. Thus far a specific role for the calcium current in early ischemic arrhythmias has only been shown in a few models and not tested in man.