Spontaneous electrical and mechanical activity was observed when single myocytes from guinea-pig hearts were loaded with sodium by direct intracellular application. Transient membrane depolarizations were found to be due to spontaneous inward currents (Isp). Both Isp and spontaneous contractions were abolished by 2',3'-benzobenzamil or 3',4'-dichlorobenzamil, two compounds that were previously reported to inhibit Na+/Ca2+ exchange. These findings suggest that the spontaneous membrane currents in Na+-loaded myocytes could be generated by the Na+/Ca2+ exchange mechanism.