We investigated the effect of hyperthyroidism and hypothyroidism on the myocardial glycogen metabolism by quantitating 125I-insulin binding, glycogen content, glycogen synthase and phosphorylase enzyme activities in the newborn rabbit. Although an increase in 125I-insulin binding was observed in response to hyperthyroidism (p less than 0.01), a decrease in myocardial glycogen (p less than 0.01) along with no change in the synthase and phosphorylase enzyme activity was demonstrated. On the other hand, propylthiouracil-induced hypothyroxinemia did not affect the 125I-insulin binding, glycogen content or the two enzyme systems. We conclude that the depletion of myocardial glycogen secondary to hyperthyroidism is independent of an increase in 125I-insulin binding or any change in the major glycogen enzyme activities (synthase and phosphorylase). We speculate that this decline in neonatal heart glycogen may be secondary to thyroxine-induced altered glucose uptake or modified postinsulin receptor events.