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The results of this study in Thailand indicate that the early response of falciparum infections to a single dose of pyrimethamine-sulfadoxine is influenced by the developmental stages of the parasite present at the time of treatment. Parasite clearance is slower when young rings predominate at the time of treatment. This should be taken into account when considering the clinical management of patients and the comparative efficacy of antimalarials in clearing parasites from the peripheral blood. The 36–48 hr delay in schizonticidal action observed after treatment of febrile infections and the associated decline in blood concentrations of pyrimethamine suggest that a single dose may not be the ideal way of administering this drug combination and may encourage the emergence of drug-resistant parasites.