Proguanil, an orally administered antimalarial drug, was given to 36 individuals (200 mg daily for 3 days). The antimalarial activity in plasma samples collected after the drug administration was then determined by bioassay. Concentrations of proguanil and cycloguanil (the principal active metabolite) in these samples were also measured by high performance liquid chromatography. A regression analysis was then performed on these variables to determine if the antimalarial activity of the samples was due to proguanil alone or to proguanil and cycloguanil together. The analysis indicated that cycloguanil is the main determinant of antimalarial activity after proguanil administration and that the activity of cycloguanil is not influenced by the presence of proguanil.