Four cases of Plasmodium falciparum malaria who presented in Sierra Leone in November-December 2000 apparently failed to respond to treatment with artesunate. Three (75%) of the cases fulfilled the World Health Organization's criteria for late treatment failure. Although artesunate ranks only sixth as the first-line drug used by clinicians for the treatment of uncomplicated malaria in Sierra Leone, it is widely sold over the counter in pharmacies in the country. The indiscriminate and injudicious use of artesunate among the Sierra Leonean population is likely to increase the level and frequency of resistance among the local strains of P. falciparum. It is recommended that artesunate be reserved for patients who fail to respond to treatment with another of the antimalarial drugs available. Even then, the artesunate should preferably be used in combination with other, longer-acting antimalarial drugs, to slow the development of further resistance.