The treatment efficacy and effects of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) on gametocyte carriage were evaluated in 181 children < or = 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug combination. All children recovered clinically. Fever clearance times were similar. The rate of P. falciparum reappearance (recrudescence or re-infection) between two and six weeks after the start of therapy was significantly higher in AL-treated children (P = 0.01). Parasite clearance was significantly faster in children treated with AL (mean +/- SD = 1.7 +/- 0.6 days, 95% confidence interval = 1.58 - 1.83, P = 0.0001) but the polymerase chain reaction-corrected cure rate (90 of 91 versus 84 of 90) and the rate of resolution of malaria-related anemia two weeks after treatment began (45 of 50 versus 33 of 46) were higher in children treated with ASP. Gametocyte carriage rates were similar. Both regimens were well tolerated. Artemether-lumefantrine clears parasitemia more rapidly than ASP but both combinations are effective in treatment of uncomplicated P. falciparum malaria in Nigerian children.