Objective: To examine the thyroid-dependence of the effect of amiodarone on the sarcolemmal Na + -K + pump, and the effect on the pump of dronedarone, a deiodinated amiodarone congener without influence on thyroid status. Methods: New Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na + -K + pump current was measured using the whole-cell patch-clamp technique in isolated ventricular myocytes. Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks. Results: Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT c ) and sinus cycle length. Na + -K + pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT c . However, it had no effect on Na + -K + pump current. Conclusions: The inhibitory effect of amiodarone on Na + -K + pump current is thyroid-dependent, whereas the effects on heart rate and QT c are at least partially mediated by thyroid-independent mechanisms. In contrast to its parent compound, dronedarone has no significant effects on the activity of the Na + -K + pump.