One hundred and fifty patients with severe falciparum malaria were administered sequential combination of dihydroartemisinin suppository followed by an oral mefloquine tablet. Dihydroartemisinin suppositories (80 mg/capsule) were given rectally once daily for 3 days with a total dose of 8-10 mg/kg. Two doses of mefloquine, 15 mg/kg/dose and 10 mg/kg/dose, were given at 72 hr and 84 hr, respectively. The mean [SD] parasite clearance time and fever clearance time were 46.1 [15.7] hr and 82.5 [59.6] hr, respectively. No death or major adverse drug effects occurred. The cure rate at 28 days of inpatient follow-up was 95% (113 of 119 patients). In severe malaria, dihydroartemisinin suppository followed by oral mefloquine is a suitable alternative treatment to parenteral drugs.