In a recent study, we have shown that the antiarrhythmic drug, amiodarone caused significant elevations of serum rT3 levels and inhibition of the peripheral conversion of T4 to T3 (Kannan et al. Endocrinology 115:1710-1716, 1984). In this study we have examined whether or not rT3 has a direct effect on the monodeiodinase enzyme activity and electropharmacology of the rabbit myocardium. Six male New Zealand White rabbits were administered 50 ug rT3 (a dose about 100 times the daily rT3 production rate) i.p. for 5 days, while the control group received saline. Serum T4, T3 and rT3 concentrations, and myocardial as well as liver and kidney 5'monodeiodinase enzyme activities were measured. Surface ECG and electrophysiological parameters in the atrial, ventricular and sinoatrial node in control and rT3 groups were obtained. Surface ECG did not show any difference in heart rate, RR, PQ, QRS or QT intervals in the two groups. Reverse T3 administration did not produce any significant alterations in APA, MRP, Vmax, APD90 and ERP of atrial and ventricular muscle. Despite administration of a massive dose of rT3, serum levels of T3 and T4 were unchanged as compared to control group. Reverse T3 administration did not produce any alterations in the 5'monodeiodinase activities in the myocardium, liver and kidney. The studies suggest that rT3 does not appreciably affect myocardial function and that the effects of amiodarone on the heart occur via mechanisms other than its ability to cause an increase in serum rT3 levels.