Sulfadoxine-pyrimethamine efficacy was determined with a 28-day follow-up in 97 children between 6 months and 15 years of age. The polymerase chain reaction (PCR)-corrected treatment failure was 8.2% and the uncorrected was 21.6%. The presence of the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) mutations linked to sulfadoxine-pyrimethamine resistance before and after treatment was determined by PCR-restriction fragment length polymorphism (RFLP) and by a fluorogenic PCR assay. Before treatment, the prevalence of the triple DHFR mutations was higher among the patients having had a recurrent parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P = 0.1). The double mutation Ala-436/Gly-437 was observed in 67% of samples, whereas no Glu-540 mutation was found. After treatment, the triple DHFR mutation was found in 76.2% of patients with recurrent parasitemia, recrudescence, and new infection alike. Such high prevalence of mutant parasites indicates that sulfadoxine-pyrimethamine should not be used as monotherapy.