Pyrimethamine was tried 17 times against Plasmodium malariae (USPHS strain) infections in 15 neurosyphilitic patients. The drug was given on one or two days in amounts totaling 25, 50, or 100 mgm. The response of the erythrocytic parasites was comparatively slow with a median of 12 days to clearance in 14 patients. Of 11 patients with an adequate follow-up, seven relapsed. Two patients who had relapsed after 25 mgm. were treated with 50 mgm. The latter dose failed to eliminate the erythrocytic parasites.