Pigmented rings are rarely observed in aestivo-autumnal fever, such parasites being caught in the capillaries as they enlarge to the stage where pigment begins to be present. Flagellated forms only develop in fresh blood preparations, 15 to 20 minutes after the taking of the blood. Of the greatest differential value is the swollen pale infected red cell of benign tertian, the normal red cell of quartan and the distorted shrunken red cell of malignant tertian. Quinine administration may cause parasites to disappear from the peripheral circulation or it may so affect the parasite that the staining would indicate a degenerated parasite—the so-called quinine-affected parasite. It is difficult to diagnose the species of malaria from such a parasite. Large mononuclears and transitionals containing phagocytized pigment (melaniferous leucocytes) are characteristic of malaria—the pigment however must be in the leucocyte and not free. There is a leucocytosis during the malarial paroxysm with a leucopenia and increase in the large mononuclears during the apyrexial period. Among natives of India the large mononuclears and transitionals averaged 21% in the apyrexial stage of malaria while healthy natives rarely showed as much as a 10% count (Stott). Some authorities have reported positive Wassermann reactions in serum of malarial patients taken during a paroxysm. All agree, however, that the serum of malarial patients at other times is negative. DIAGNOSIS In the diagnosis of malaria the special points to consider are: (1) presence of malarial parasites, (2) periodicity, (3) splenic enlargement, (4) response to quinine therapy, (5) the presence of melaniferous leucocytes and (6) a high large mononuclear percentage when leucopenia is present. In the examination for parasites one should not only consider the species of parasite present but, as well, the stage of development and the presence of the sexual forms. In an intensive investigation Bass has shown that 55.09% of those showing parasites in the blood give a clinical history of malaria while 44.91% of those with parasites in the blood fail to be associated with clinical manifestations. Blood platelets are the findings most frequently mistaken for malarial parasites in stained blood, and the vacuoles in fresh blood. Quartan and tertian periodicity is only found in malaria, but quotidian periodicity is a feature of a host of diseases. There are very few tropical diseases which have not been mistaken for malaria and many of these have been considered as of malarial etiology before the discovery of the real cause. Of the cosmopolitan diseases, typhoid fever, septic conditions, including malignant endocarditis, tuberculosis, influenza, pyelitis and even syphilis are to be considered in a diagnosis of malaria.