The efficacy of a 12-mg/kg (of body weight) intramuscular amopyroquin (ApQ) regimen (two successive 6-mg/kg injections at a 24-h interval), previously established from kinetic studies on healthy volunteers and multicenter studies on patients with malaria, was investigated in 152 patients (children and adults) in Gabon with Plasmodium falciparum malaria. All children in the present study (ages, 1 to 14 years) showed higher degrees of parasitemia and temperatures and lower hematocrit values than did adults at the time of admission. No major side effects in the patients were observed. On day 7, all patients were apyretic; clearance of parasites was obtained in 143 of 152 patients (94%); a low level of parasitemia was observed in nine patients, all of whom were children (6%). In vitro chemosusceptibility tests carried out on P. falciparum isolates from patients demonstrated 51% of resistance to chloroquine (Cq). A correlation was found between the in vitro chemosusceptibilities to Cq and ApQ, but no relationship between the in vitro activity and the in vivo efficacy of ApQ could be found. Concentrations of ApQ in blood assayed by high-performance liquid chromatography on day 2 did not differ significantly between the groups in whom therapy was a success or a failure, although the mean ApQ concentration in blood for the group that failed therapy was 31% lower. Concentrations greater than 100 nmol of self-prescribed Cq and amodiaquine per liter, which were assayed simultaneously with ApQ, were observed in 78 patients (51%). They did not correlate with degrees of parasitemia compared with ApQ alone, which did. Successful treatment by day 7 was obtained in 69 of 74 patients (93%) who had no other 4-aminoquinolines in their blood. The results of the present study show that an ApQ regimen of 12 mg/kg over 2 days may be an alternative for the treatment of Cq-resistant malaria, at least in adult patients, in the field.