1. The immediate tissue reaction of the body to the malaria plasmodium consists in a stimulation of the reticulo-endothelial apparatus (system of histiocytes), leading to a new formation of macrophagic tissue in various organs. Both the specific endothelia of the liver, spleen, lymph nodes, and bone marrow; and the histiocytes of the connective tissue take part in the stimulation.2. In therapeutic malaria the blood histiocytes are mainly derivatives of the specific endothelium. To a minor degree common capillary endothelium is engaged in the formation of intravascular endothelial phagocytes. This has been established for the endothelium of the capillaries of the brain cortex and for the endothelial cells of the capillary venules of certain connective tissues.3. By means of the supravital technique, it has been found that the intravascular macrophagic phagocytes are clasmatocytes in the sense of Sabin, Doan, and Cunningham.4. The capillary endothelial cells, although they show signs of stimulation, do not become phagocytic while they retain their anatomical position in the vessel wall.5. Besides involving the histiocytes there is an activation of the undifferentiated embryonic mesenchymal cells.6. The fibroblast, the mesothelial cell, and the histiocyte are distinct types of cells. While both the fibroblast and the mesothelial cell are also capable of stimulation, they still can be distinguished from the active histiocyte in malaria-infected tissue.7. In the nervous system the macrophagic response has been greatest in the leptomeninges. In the arachnoid the malaria-stimulated histiocyte stands out distinctly from the less active arachnoidal lining cell.8. In the adventitial sheaths of the vessels of the brain cortex the mesodermal phagocytes are only slightly stimulated. About middlesized and large cortical vessels a small increase in the number of macrophages has been found. In the perivascular spaces of the large vessels in the white matter, and in the striatum, and in the pons, stimulated histiocytes are more numerous. The small mesodermal elements along the capillaries of the brain cortex have not been seen to be activated.9. The microglia, as a whole, does not take part in the general reaction of the reticulo-endothelial system.10. Therapeutic malaria produces an activation of the mesodermal tissue in which the stimulation of the histiocytes and the activation of the undifferentiated mesenchymal cells are outstanding features.