The pharmacokinetics of amodiaquine (AQ, Flavoquine, CAS 6398-98-7) and its metabolites, mono (AQml) and bis-desethyl amodiaquine (AQm2) were investigated in 8 healthy volunteers after an oral dose of 306.2 mg of AQ. Metabolic clearance was the main AQ elimination pathway. AQ disappeared rapidly, from the plasma and blood, whereas AQml appeared rapidly in keeping with a hepatic first-pass effect. By contrast, AQ was little excreted in urine and AQm2 formation from AQm1 was low. Blood AQm1 concentrations were higher than plasma levels, with an AQm1/AQ concentration ratio of 5 to 10. This result was related to strong uptake of AQm1 by white blood cells, as shown by an in vitro study. On the basis of plasma concentrations, there was no preferential uptake by red blood cells, the pharmacological target cells; effective AQ concentrations should thus be analyzed in plasma rather than in whole blood. The inhibitory activity of patients' sera on Plasmodium falciparum growth in vitro appears to be directly related to the AQm1 concentration.