In spite of important advances in cardiology in recent years, pharmacological control ofcardiac arrhythmias in the clinic remains an experiment conducted on a patient-by-patient basis using a trial and error approach tempered by good clinical judgment. Treatment, especially of life-threatening ventricular arrhythmias, remains largely empiric today because of our lack of understanding of the complex pathophysiological processes that give rise to cardiac rhythm disturbances. The problem is com-pounded by our incomplete understanding of the mechanisms by which antiarrhythmic agents act to suppress and in some cases aggravate arrhythmias. Also confounding is the lack of criteria that can be applied to the differential diagnosis of specific ar-rhythmia mechanisms in the clinic. Differential diagnosis of cardiac arrhythmias re-quires an understanding of basic mechanisms and establishment of mechanism-specific electrophysio-logical criteria. Both in turn depend on our knowl-edge of the basic electrophysiological characteristics of the cells and tissues of the heart and the extent to which heterogeneity or specialization exists. Our ability to design specific drug treatments also de-pends on our understanding and awareness of differ-ences in the pharmacological responsiveness of di-verse cell types within the heart. Until recently, most investigations of the electro-physiology and pharmacology of the ventricles focused on two main cell types, namely, ventricular myocardium and Purkinje fibers (or conducting tis-sues). Recent studies have provided data supporting the existence of at least four functionally distinct cell types in the canine ventricle, each with a characteristic electrophysiological and pharmacological pro-