There are few safe, effective chemoprophylactic regimens for preventing Plasmodium falciparum infection in south-east Asia. In two randomized placebo-controlled trials, combinations of proguanil and sulphonamide were tested for chemoprophylactic activity in schoolchildren, aged 6-15 years, living near the Thai-Burmese border. Proguanil at an equivalent adult dose of 200 mg/d was combined with sulphafurazole (= sulfisoxazole) at 25 mg/kg/d or sulphamethoxazole at 25 and 10 mg/kg/d. Combinations of daily proguanil/sulphafurazole and proguanil/sulphamethoxazole were equally effective (greater than 75%) against both falciparum and vivax malaria when the sulphonamide component was used at 25 mg/kg/d. Proguanil and sulphamethoxazole at 10 mg/kg/d was ineffective. Approximately 1% of the children had sulphonamide-related skin rashes which resolved when treatment stopped. Proguanil/sulphonamide is a possible alternative chemoprophylactic regimen in areas with multiple drug-resistant P. falciparum.