One hundred and two Thai patients with severe falciparum malaria (92 males and 10 females) were allocated at random to receive either the standard regimen of quinine infusion (52 cases) or intramuscular artemether (50 cases). The patients in both groups had comparable admission clinical and laboratory data. Artemether gave a better survival rate (87.2% vs. 63.3%) and parasite clearance time (54 vs. 78 h) than quinine. Fever clearance times (79 h vs. 84 h) and time to recovery of consciousness (48 h in both groups) were comparable. Previous treatment with quinine or mefloquine had no influence on treatment outcome. The most common adverse effect in patients treated with quinine was tinnitus. Two patients had severe hearing impairment which resolved within 1 week after the end of treatment. Mild, transient pain was noted at the injection site of artemether but no abscess formed. QTc wave prolongation was seen in most patients receiving quinine; however, no arrhythmia was observed despite the high concentration of quinine in some patients who had received quinine before admission. Complications developed in 7 survivors in each treatment group. No patient in the artemether group had neurological sequelae after recovery of consciousness, but 2 in the quinine group had left facial palsy and one had a myasthenia gravis-like syndrome. No patient died with complications in he artemether group, but 7 died with pulmonary complications in the quinine group.