Studies have been made of the effects of cortisone on the course of primary and developed infections with P. cynomolgi in the rhesus monkey. This investigation has shown that repetitive admmistration of the hormone in daily doses of 10 mg. per kg. during the primary attack produced striking intensification of the peripheral blood infection during the postcrisis phases of the disease. Similar administration of 10 or 50 mg. per kg. doses of the hormone during the chronic or latent stages of the infection provoked recrudescences of remarkable severity. In both early and late infections the responses induced by cortisone treatment corresponded closely to the reactions to splenectomy. Collateral studies have shown that the doses of cortisone which produced the reactions described above also evoked a lymphopenia, marked reductions in the sizes of the axillary and inguinal lymph nodes and spleen, and striking histological changes in the latter organ. These changes involved severe regression or exhaustion of lymphoid elements in both splenic nodules and pulp with almost complete obliteration of proliferative activities involved in the production of macrophages from lymphocytes. Indications are that the resulting reduction in supply of macrophages, rather than inhibition of phagocytic activity per se, was responsible for the intensification of the disease produced by cortisone.