Injections of 1 or 2 mg doses of cortisone, hydrocortisone, corticosterone or prednisolone into mice cause, 24 h after the injection, a large decrease in weight of spleen and thymus which is accompanied by very large increases in the activity of the lysosomal acid phosphatase in these tissues. Prednisolone and hydrocortisone were most effective. Injection of testosterone, 11-hydroxyprogesterone and 17-hydroxyprogesterone had very little effect on the weight of the lymphoid tissues and caused only very small changes in the activity of lysosomal enzymes. These effects of the activating hormones are very similar to those previously observed following irradiation of the spleen or thymus with X-rays. The lysosomal activation observed is probably mediated by lymphocytolysis and not by a direct effect of the steroids on the lysosomes.