Glucocorticoids have been used in the treatment of a number of diseases where immunological intolerance plays a predominant role. Since immunological intolerance points to the involvement of lysosomal enzymes and glucocorticoids are known to affect their activities, we have attempted to study the effect of these steroids on cardiac and renal enzymes. Dexamethasone, a glucocorticoid, is administered subcutaneously to male Wistar rats at a dosage of 2.5 mg/kg/week on alternate days for two weeks. After withdrawing the steroid, the animals are monitored for one week to oversee the recovery process. Total and free activities of glycohydrolases and cathepsins in serum, heart and kidney are assayed on the days 4, 8, 12, 16 of dexamethasone administration and also on days 4 and 8 following discontinuation of the steroid. During dexamethasone administration, a significant decrease in both the free and total activities of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, alpha-galactosidase, alpha-mannosidase, cathepsin B and cathepsin D are observed in heart and kidney, but the enzyme levels are shown to increase in serum. On withdrawal of the steroid, the activities of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase are found to be increased in heart and kidney, whereas, the activity of alpha-mannosidase remains within normal values. Thus, it could be seen that dexamethasone alters the pattern of glycohydrolases and cathepsins, which are involved in protein degradation.