Quinine disposition was studied in 5 subjects before and during an experimentally induced infection with a chloroquine-resistant strain of Plasmodium falciparum and in 2 individuals before and during artificially induced fever. Plasma quinine levels were determined by both a benzene extraction method (QB), which measures principally unmetabolized quinine, and a metaphosphoric acid precipitation method (QMPA), which measures quinine and quinine metabolites. The ratio QB/QMPA in plasma was used to estimate the extent of metabolism of quinine. In all individuals plasma levels of quinien and QB/QMPA ratios were increased during malaria, suggesting impaired hepatic metabolism of quinine. The changes observed during malaria were not due to altered renal excretion of quinine. In 2 subjects in whom fever was artificially induced there were similar changes in quinine metabolism. These observations suggest that quinine dosage should be modified during the initial period of treatment, when symptoms and fever are greatest, in acute falciparum malaria.