The physiological effects of steroid hormones are thought to be mediated by an initial obligatory step of binding to stereospecific intracellular receptor proteins in target tissues. Highaffinity glucocorticoid receptors have been demonstrated in adrenalectomized rat and dog heart by the specific binding of dexamethasone (DM). By Scatchard plot analysis, the equilibrium (dissociation) constant of the 3HDM-cytoplasmic receptor complex in both species was 3 × 10-9M (0 C) ; the concentration of binding sites was 1.3 × 10-13M per mg cytosol protein in the dog heart and 4.0 × 10-13M per mg cytosol protein in the rat heart. The affinity of these receptors is in the order corticosterone progesterone aldosterone testosterone estradiol. Tritiated aldosterone was also shown to be bound in rat and dog heart cytosol; this binding is specific in the sense that binding of tracer was shown displaceable by excess unlabeled aldosterone. In the heart, however, as opposed to the kidney, such binding of 3HA is better displaced by unlabeled corticosterone than by equivalent levels of unlabeled aldosterone itself. The higher affinity of corticosterone than aldosterone for cardiac 3HA binding sites suggests that 3HA is binding to glucocorticoid receptor sites in the adrenalectomized experimental animal. Experimental cardiac effects of both mineralocorticoid and glucocorticoid hormones have been reported by various authors. In the present study, no physiologically specific mineralocorticoid receptors comparable with those in the kidney could be detected in cardiac cytoplasm. The finding of specific glucocorticoid receptors in the heart, on the other hand, supports the possibility of a direct glucocorticoid action on cardiac function. (Endocrinology93: 1300, 1973)