Aim The study of the mechanisms underlying the oscillatory afterpotential (V os) and prepotential (ThV os). Background It has been recently shown that V os and ThV os play an obligatory role in the dominant sinoatrial node (SAN) discharge. Methods Guinea pig isolated SAN was studied in vitro by means of a microelectrode technique. Results High [K +] o and premature stimuli unmask V os superimposed on early diastolic depolarization and ThV os within a less negative voltage range (“oscillatory zone”). Subthreshold stimuli elicit ThV os in the oscillatory zone, but not at more negative values. Drive and caffeine shift the oscillatory zone in a negative direction. Low caffeine concentrations increase the size of V os and of ThV os, rate, and force. High caffeine concentrations suppress V os but increase the size of ThV os and shift them to more negative values until they eventually miss the threshold. In quiescent SAN in high caffeine, a fast drive enhances ThV os size, thereby initiating a transient spontaneous rhythm (“overdrive excitation”). Adrenergic agonists potentiate caffeine-induced overdrive excitation through an increase in ThV os. In high caffeine, the first twitch after quiescence is not larger, twitch relaxation is slower, V os is abolished, and the prolonged nonoscillatory afterdepolarization V ex is induced, consistent with an impairment of Ca 2+ handling by the sarcoplasmic reticulum. The effects of caffeine in Tyrode's solution are accounted for by the caffeine-induced changes in the oscillatory potentials. Tetrodotoxin decreases force and size of both V os and ThV os. Conclusions The mechanism underlying V os is related to a diastolic release of Ca 2+ from a Ca 2+-overloaded sarcoplasmic reticulum, whereas that of ThV os appears to be related to ionic currents in the resting potential range that can initiate and sustain spontaneous discharge.