In the research carried out in a hyperendemic zone of Nigeria, 42 non-immune patients with P. falciparum malaria were treated with combinations of antifolic drugs in a single administration. 22 patients received a combination of sulfametho- pyrazine and trimethoprim (group ST); 20 patients received a combination of sulfametopyrazine and pyrimethamine (group SP). On the day of diagnosis and for 5 successive days after the beginning of treatment, peripheral blood, fever and various other findings characteristic of malaria were checked. In 22/22 patients of group ST and 18/20 patients of group SP, the suppression of malaria was obtained within a short time; 2 patients of group SP still had parasites, but very reduced in number, in the blood on 5th day. After 2–9 months of observation, none of the patients of either group had clinical manifestations referable to malaria.