Alterations in plasma electrolyte concentrations were produced by potassium deficiency, by adrenalectomy and by administration of cortisone and Adrenalin. The effect of these procedures on thigh and stomach muscle electrolytes was compared. Differences in response of the two types of muscle were analyzed and the conclusion drawn that different mechanisms control electrolyte composition of smooth and skeletal muscle. Implications of this are discussed. Calculations are presented which suggest that cortisone and Adrenalin enhance the potassium concentrating ability of skeletal muscle cells and that Adrenalin, in addition, restores the ability of muscle cells from adrenalectomized animals to exclude sodium.