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To examine the clinical and parasitologic efficacy of quinine, we studied 34 children (7 months–13 years old) with severe or moderately severe Plasmodium falciparum infections. Quinine 10 mg/kg every 8 hr for 3 days was administered, initially by intravenous infusion of quinine formate followed by oral quinine dihydrochloride when tolerated. Thirty-three of the 34 patients were clinically well and had negative malaria smears 7 days after the initiation of therapy; 1 child, who presented in coma, died 29 hr after enrollment. The mean fever clearance time was 44.1 hr, and the mean parasite clearance time was 59.6 hr. A mean peak quinine level of 9.7 ppm was attained after the second dose of quinine, and the minimum concentration was maintained at 5–7 ppm during the 2nd and 3rd hospital days. In vitro testing was conducted with parasites from 10 patients: 9 isolates were resistant to chloroquine, and inhibition of schizont development with quinine occurred at a concentration of 8–32 pmol/well.