Multidrug resistance of Plasmodium falciparum is becoming common in Africa. In a randomized trial, four short-term regimens were compared for treating uncomplicated P. falciparum malaria in children 4-15 years old in Gabon. One hundred thirty patients received chloroquine (25 mg/kg over 48 h; group C), chloroquine (as above) plus clindamycin (5 mg/kg every 12 h for 6 doses; group CCl), quinine (12 mg/kg every 12 h for 6 doses; group Q), or quinine (as above) plus clindamycin (as above; group QCl). In group C, only 9% of patients were cured by day 28, 44% showed recrudescent malaria (RI), and 47% showed intermediate or high-grade resistance (RII/RIII). In group CCl, 70% of patients were cured and 30% showed recrudescences. In group Q, 32% were cured and 68% showed recrudescences. In group QCl, 88% were cured and 12% showed recrudescences after day 14. All treatment regimens were well tolerated. Thus, the combination of clindamycin with chloroquine or quinine enhances parasite clearance and improves response to therapy.