The susceptibility in vivo of Plasmodium falciparum to mefloquine, mefloquine/sulfadoxine/pyrimethamine and chloroquine was investigated in 115 children with acute uncomplicated falciparum malaria. Susceptibility of P. falciparum isolates to mefloquine and chloroquine in vitro was also investigated. Mefloquine alone and mefloquine/sulfadoxine/pyrimethamine showed similar response rates and both reduced parasitaemia and fever more rapidly than chloroquine. Mefloquine also promptly reduced parasitaemia and fever within 48 h in all chloroquine treatment failures. In vitro, 10% of isolates showed reduced susceptibility to mefloquine and 18% were resistant to chloroquine. These results suggest that the addition of sulfadoxine/pyrimethamine does not have a significant therapeutic advantage over mefloquine alone in the treatment of acute uncomplicated falciparum malaria in children from this endemic area.