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Genetic polymorphisms in Plasmodium falciparum are associated with resistance to a number of drugs, but data on their prevalence are limited from many areas. We explored the prevalence of key polymorphisms in patients presenting with malaria in Kinshasa. Prevalences of pfcrt K76T; pfmdr1 N86Y; pfdhfr N51I, C59R, and S108N; and pfdhps A437G were well above 50% and of pfmdr1 Y184F, N1042D, and D1246Y; pfdhfr I164L; and pfdhps K540E were low. These results suggest an intermediate level of resistance to aminoquinoline and antifolate antimalarials in Kinshasa compared with other areas of Africa.