The effect of cortisone administration on two lysosomal enzymes of rat heart and skeletal muscle has been studied. Activities of acid phosphatase and β-glucuronidase were assayed in homogenates and in partidulate and supernatant fractions. Free and total acid phosphatase activity was measured in liver homogenates. Both enzymes were particulate bound and detergent activated indicating the existence of lysosomes in heart and skeletal muscle. However, these enzyme activities were quite as low compared to those in liver. Single or multiple doses of cortisone acetate had no significant effect on any of the enzyme measurements, suggesting that the number and permeability of lysosomes were unchanged in these tissues by cortisone. The possibility that lysosomes are not involved in the physiological control of protein metabolism in muscle cells is discussed.