The underlying mechanism commonly applicable for both the positive and negative force-frequency relationships (FFR) was pursued in left atria (LA) of rat and rabbit. The species differences in the roles of Na/Ca2 exchanger and sarcoplasmic reticulum (SR), which are major intracellular Ca2 regulatory mechanisms in the heart, were examined in the amplitude accommodation to the frequency that changed from 3 Hz to the variable test frequencies for 5 minutes in the electrically field stimulated left atria (LA) of rat and rabbit. Norepinephrine strongly increased the frequency-related amplitude accommodation in both of rat and rabbit LA, while monensin, oubain or the reduced Na and 0 mM Ca2 containing Tyrode solution increased the frequency-related amplitude accommodation only in the rabbit LA. Monenisn was also able to increase the frequency-related amplitude accommodation only in 1-day old rat LA but not in 4-week old rat LA that had 75% less Na/Ca2 exchanger with 97% higher SR than 1-day old rat LA. Taken together, it is concluded that the differences in the prevalence between myocardial Na/Ca2 exchanger and SR in the amplitude accommodation to the frequency-change determine the difference in the FFR between rat and rabbit heart.