BACKGROUND: Cerebral malaria has a mortality rate of 10 to 30 percent despite treatment with parenteral quinine, a situation that may worsen with the spread of quinine resistance. Artemether is a new antimalarial agent that clears parasites from the circulation more rapidly than quinine, but its effect on mortality is unclear. METHODS: We conducted a randomized, unblinded comparison of intramuscular artemether and intramuscular quinine in 576 Gambian children with cerebral malaria. The primary end points of the study were mortality and residual neurologic sequelae. RESULTS: Fifty-nine of the 288 children treated with artemether died in the hospital (20.5 percent), as compared with 62 of the 288 treated with quinine (21.5 percent). Among the 418 children analyzed at approximately five months for neurologic disease, residual neurologic sequelae were detected in 7 of 209 survivors treated with artemether (3.3 percent) and 11 of 209 survivors treated with quinine (5.3 percent, P = 0.5). After adjustment for potential confounders, the odds ratio for death was 0.84 (95 percent confidence interval, 0.53 to 1.32) in the artemether group, and for residual neurologic sequelae, 0.51 (95 percent confidence interval, 0.17 to 1.47). There were fewer local reactions at the injection site with artemether than with quinine (0.7 percent vs. 5.9 percent, P = 0.001). CONCLUSIONS: Artemether is as effective as quinine in the treatment of cerebral malaria in children.