It has been shown that thyroid hormone has a significant effect on the heart and that suppression of thyroid function may contribute to the antiarrhythmic effect of amiodarone. The study was aimed at investigating the effects of hypothyroidism, compared with those of amiodarone, on vulnerability to ventricular fibrillation in dogs. In this study, 25 adult dogs were randomly divided into three groups: a hypothyroid group following total thyroidectomy (n = 9), an amiodarone group (n = 8, 400 mg per day, 4 weeks), and a control group (n = 8). Both amiodarone and control groups were subjected to sham surgery. Five to 8 weeks after surgery, ventricular fibrillation threshold and other electrophysiological parameters were determined. Right ventricular effective refractory period, monophasic action potential duration, and ventricular fibrillation threshold were significantly increased in both the thyroidectomized and amiodarone-treated animals. There was no significant change in monophasic action potential duration dispersion. The incidence of ventricular fibrillation during ischemia and reperfusion was significantly reduced in both treated groups compared with the sham-operated euthyroid controls. These observations suggest that hypothyroidism has a significant antifibrillatory effect in dogs. Homogeneous prolongation of repolarization and refractoriness may contribute to the antifibrillatory action of hypothyroidism.