The initiation and modulation of the heartbeat are important areas of common interest to physiologists and cardiologists. It is only very recently, however, that technical advances have made possible quantitative investigations of the ionic events underlying the initiation of cardiac excitation so that the mechanisms of pacemaking are now beginning to be unraveled. When single-microelectrode recording from cells within the intact pacemaker region was the only electrophysiological technique available, the cardiac pacemaker potential was considered to be regulated by three different factors: the slope of the slow diastolic depolarization, the maximum diastolic potential, and the threshold of activation of the spike potential. Early experiments showed that the slope of the slow diastolic t Deceased 19 November 1991. depolarization is affected by changes of extracellular Na+ concentration ([Na+] J, temperature, and sympathetic agonists and that the maximum diastolic potential is influenced by efferent vagus nerve activity. Both the slope of the diastolic depolarization and the maximum diastolic potential were shown to depend on the K+ conductance that is activated during the action potential and decays during the pacemaker depolarization, and the threshold of depolarization was shown to be affected by changes in [Ca”‘],. To understand the basis of pacemaker rhythmicity in more detail, it is necessary to study the voltage-and time-dependent properties of the ionic currents underlying the electrical activity of the pacemaker cells. In principle, the voltage-clamp method can provide this information. Once voltage-clamp methods have been applied to sinoatrial (SA) node preparations and ionic currents have been measured, it is possible to investigate the factors affecting individual currents. It has become clear that explanations of the regulation of pacing