1. (45)Ca fluxes were studied in normal and potassium-depolarized goldfish ventricles as a function of the external Na concentration. Some of the experiments were also performed on guinea-pig auricles.2. When the external K concentration was increased from 5.4 to 142 mM, keeping osmolarity constant by adding 137 mM-Li or choline (hyperosmotically) to the low K solution, the (45)Ca efflux was reversibly inhibited, whereas the [(3)H]sucrose efflux was unaffected.3. Goldfish ventricles, which have been depolarized with 142 mM-K for 100 min, repolarized within 20 min, from ca. -15 mV to ca. -70 mV, following the application of 5.4 mM-K. This repolarization was independent of the presence of external Na. During the repolarization the (45)Ca efflux was reactivated. This reactivation, however, depended on the external Na concentration. Comparable results were obtained in guinea-pig atria.4. A similar repolarization and Na-dependent reactivation of (45)Ca efflux was obtained in goldfish ventricles superfused with 10(-6) M-Ca(2+) (4.5 mM-Ca, 5 mM-EGTA, pH 7.1), provided that the (45)Ca washout was started in high K.5. In 10(-6) M-Ca(2+), 137 mM-Na, 5.4 mM-K and 137 mM-choline goldfish ventricles depolarized to about -25 mV within 80 min. If the choline was now replaced by 137 mM-K, the membrane potential moved to ca. -15 mV, and under these conditions the (45)Ca efflux was slightly increased.6. Following Na-free perfusion for 100 min, and at normal external Ca concentrations, the (45)Ca efflux from goldfish ventricles was stimulated by the addition of Na. The curve relating this stimulation to the external Na concentration had a sigmoidal shape and was shifted to the right by K-depolarization. In guinea-pig atria the inhibition of the Na-stimulated Ca efflux by depolarization was of a non-competitive type.7. Following a Na-free incubation of 100 min and a subsequent period of 20 min in 137 mM-Na, the intracellular Na content of goldfish ventricular cells was some 20% lower in K-depolarized cells than in cells at the resting potential.8. (45)Ca influx in goldfish ventricles in the presence of 137 or 68.5 mM-Na was not significantly changed by K-depolarization.9. The results show that the Na-dependent fraction of Ca efflux is inhibited by high external K. The effect is probably due to depolarization, which may be an argument in favour of electrogenic n Na(+)-1 Ca(2+) exchange, with n >/= 3.