Mayotte is a French island located in the Comoros archipelago in the Indian Ocean. Due to the high level of resistance to chloroquine and sulfadoxine-pyrimethamine in this area, new therapeutic strategies are required. The aim was to assess and to document the efficacy of artemether-lumefantrine (AL) combination in four oral dosages. The follow-up was carried out during 21 days to monitor the antimalarial drug efficacy in an open trial in April-May, 2002. Results were obtained from 51 patients, aged from three to 46 years (12% less than five years). No case of therapeutic failure was observed. At day 2 after treatment, all the patients were apyretic and none of them had parasitaemia until day 21. This first therapeutic trial of the AL combination in the Indian Ocean sub-region shows that this association is safe, effective and rapid. AL should be an alternative treatment of uncomplicated malaria attacks in Comoros Archipelago, and will be of help to manage imported chloroquine-resistant falciparum malaria strains in Madagascar.