Calculated therapeutic doses of digitalis and its derivatives did not produce demonstrable microscopic changes in the myocardium of experimental animals. Toxic doses of digitalis (twice a therapeutic dose) induced myocardial lesions in animals. In those animals with experimentally induced mild to moderate hyperthyroidism, calculated therapeutic doses of digitalis did produce myocardial lesions. Toxic doses of digitalis administered to animals with mild to moderate hyperthyroidism caused extensive degenerative changes in the myocardium or promptly killed the animals without associated microscopic lesions.