A cytochemical and biochemical study was made of lysosomal changes in epithelial cells of mouse thymus before and after hydrocortisone treatment. In untreated mouse thymus, acid phosphatase is present mainly in the golgi vesicles and occasionally in lysosomes. There is a delayed lysosomal response (12 hours) after treatment, with acid phosphatase activity reaching its maximum during the peak of involution (18-36 hours). During this period most of the enzyme activity is confined to the lysosomes. The pattern of distribution of histochemically demonstrable lysosomal enzymes bears a close resemblance to that of PAS positive bodies. It has been postulated that the lymphopoietic stimulating factor(s) is secreted in these PAS positive structures. On the basis of this assumption, it is suggested that lysosomal enzymes which are found to be present in the secretory vacuoles mediate the breakdown and release of this factor(s), in the manner of other endocrine glands. © 1969 Springer-Verlag.