[3H]Dexamethasone binding capacity in rat muscle cytosol was determined after various endocrine manipulations in an attempt to identify factors which might regulate the level of the cytoplasmic hormone receptor proteein. Hypophysectomy and adrenalectomy markedly increased the specific binding of [3H]dexamethasone in skeletal muscle cytosol, while implantation of the MtT tumor which secretes ACTH and growth hormone, as well as treatment with glucocorticoids reduced the glucocorticoid specific binding. Since the effects of hypophysectomy and the MtT tumor depend on the presence of the adrenals, they appear to be mediated via changes in circulating glucocorticoid level. Alloxan- or streptozotocin-induced diabetes caused only a slight reduction in the binding of [3H]dexamethasone in muscle, suggesting that the enhanced responsiveness to glucocorticoids in diabetes is not due to increased glucocorticoid receptor activity. There is a sex-dependent effect on binding, female rats having a higher concentration of binding sites. Treatment with the synthetic androgen fluoxymesterone or with glucocorticoids reduces binding, while estradiol-17.beta. enhances it. The changes in glucocorticoid binding capacity induced by the various endocrine manipulations appear to reflect mainly changes in receptor concentration rather than occupancy, since the binding assays were preformed after a suitable time allowance for removal of the administered hormones by metabolism.