In the face of spreading chloroquine and sulfadoxine-pyrimethamine (SP) resistance, amodiaquine remains a cheap and efficacious alternative for treating uncomplicated Plasmodium falciparum malaria in many settings. In Harper, south-eastern Liberia, a previous study we conducted showed very high levels of resistance to both chloroquine and SP. In 2001, in an effort to look for possible alternatives, we measured in the same setting the efficacy of amodiaquine in a 28-d study in vivo, with results corrected by polymerase chain reaction genotyping to distinguish recrudescences from reinfections. In total, 107 children were included in the study and received a 3-d supervised course of 25 mg/kg amodiaquine. Of these, 81 were analysable at day 28. The overall failure rate was 19.8% (95% CI 11.7-30.1%) considering both parasitological and clinical outcomes. These results provide hitherto missing data on amodiaquine in Liberia, and confirm that the drug may still be efficacious in settings where chloroquine and SP are failing. We recommend the introduction of amodiaquine in association with artesunate as a first-line antimalarial in Harper.