The classical idea that selenium is toxic to the heart at levels higher than available in a balanced diet is not supported by experimental work. In mice, treatment with sodium selenite increased the LD50 of ouabain and 2,4-dinitrophenol, and increased the tolerance to nitrogen inhalation. Although sodium selenite had no effect on the dog heart with circulation intact, there was a reduction in coronary vascular resistance in the heart-lung preparation. In the isolated ventricular segment perfused with blood, the administration of sodium selenite caused a positive inotropic effect which appeared even after blockade of beta-adrenergic receptors and in segments perfused with a Krebs-bicarbonate solution that was deficient in oxygen. These results cannot be explained merely as the correction of a selenium deficiency but rather as a positive influence of sodium selenite on the heart that has been acutely stressed by oxygen lack, ouabain, or 2,4-dinitrophenol.