The influence of the Na-Ca exchange (NaCaX) on the effects of rest (30-300 s) on twitch amplitude and SR Ca content (assessed by caffeine contractures) was studied in ventricular myocytes isolated from rat and rabbit. In control conditions, rabbit cells showed monotonic rest-decay of the amplitudes of both twitch and caffeine contractures, while rat myocytes developed rest-potentiation of twitches without change in SR Ca content. Inhibition of the Na-Ca exchange during rest by perfusion with 0Na,0Ca solution did not affect the responses in rat cells but abolished rest-dependent SR Ca loss in rabbit cells. Indeed, when NaCaX was blocked during rest, then rabbit cells, like rat, displayed rest-potentiation of twitches. Stimulation of net Ca extrusion via NaCaX during rest by perfusion with 0Ca solution induced rest-decay of twitches and caffeine contractures in rat cells similar to that observed in rabbit cells. This maneuver also accelerated decline in SR Ca during rest and amplitude of the first post-rest twitch in rabbit myocytes. These effects were only slightly enhanced by preperfusion with 0Na,0Ca solution to deplete Nai. We were thus able to interconvert the contractile responses to rest between these cell types solely by modifying the driving force for Ca transport by the exchange. Our results indicate that SR Ca is lost during quiescence in both species, but only if the NaCaX is able to promote diastolic Ca extrusion will net decline of SR Ca (and twitch amplitude) occur. On the other hand, post-rest twitch potentiation in both rat and rabbit cells can occur without a change in SR Ca content. This effects might be attributable, at least in part, to a slow phase of recovery of excitation-contraction coupling.