The events caused by overdrive-induced calcium overload were studied in guinea pig isolated ventricular myocytes. Overdrive may induce oscillatory potentials (V<sub>os</sub>) and a prolonged depolarization (V<sub>ex</sub>), as well as the underlying currents (I<sub>os</sub> and I<sub>ex</sub>, respectively). Acetylcholine (ACh) reduced or abolished these events, an action which was blocked by atropine. Norepinephrine exaggerated the effects of overdrive, and ACh markedly antagonized such an enhancement. Caffeine at low concentrations increased both I<sub>os</sub> and I<sub>ex </sub>whereas at high concentrations caffeine abolished I<sub>os</sub> but increased I<sub>ex</sub>. Quinacrine abolished both events. Voltage clamp depolarizing steps abolished I<sub>os</sub> (and did not reverse it). Thus, the effects of Ca overload are antagonized by ACh in the absence and presence of sympathetic enhancement. Also, the mechanism underlying I<sub>os</sub> appears to involve an electrogenic Ca extrusion and not an increase in a nonspecific conductance.