Plasmodium falciparum susceptibility to halofantrine hydrochloride was investigated in a small village near Ouagadougou, Burkina Faso, where the parasite was known to be chloroquine resistant. An in vivo test was carried out in July 1992 at the beginning of the rainy season in children ranging in age from two to eight years with P. falciparum monospecific infections, asexual parasitemia greater than 800/microliters of blood, and a negative result on a Bergqvist urine test for 4-aminoquinolines. Among 206 children screened, 74 were selected for study. Blood samples were collected on days 0, 2, 4, 7 and 14, and 100 microscopic fields of thick and thin blood smears were examined for parasite density and species identification. Halofantrine hydrochloride was administered under supervision at the standard dose of 24 mg/kg as 8 mg/kg given three times at 6-hr intervals with an observation period of 1 hr after each 8-mg/kg dose. Parasitemias cleared in all 74 cases by day 7, but there was a recurrence of parasitemia in six subjects (8.1%) on day 14. A second course of therapy with halofantrine resulted in prompt clearance of parasitemias in all of these children. The drug was well-tolerated and the hematologic and biochemical indices were not adversely affected by treatment.