The combination of a long acting sulfonamide, Sulfametoxazol, and a dihydrofolic acid redutase inhibitor, Trimethoprim, was employed in the treatment of 40 cases of natural infections falciparum malaria chloroquine resistant, according to two schedules. On a first group of 20 patients with poor clinical manifestations and low parasitis average, sulfametoxazol (0,800 gm) plus trimethoprim (0,160 gm) were administered in single dose to 10 patients and during two days, to 10 others. The clearance of asexual parasits occurred in all cases, however, 6 of 13 presented relapses during the cure control period of 30 days. No side clinical manifestations were observed in this group. On the second stage 20 cases most of them also chloroquine - resistant with severe clinical manifestations were treated with sulfametoxazol (1.600 gm) plus trimethoprim (0,320 gm) daily for four days. Clearence of trofozoits occurred in all cases during a time of 36 to 96 hours after therapy. Relapses occurred in 2 cases. Megaloblastic anemia occurred in 1 patient who recovered spontaneously.