Abstract 373 subjects occupationally exposed to high levels of malaria transmission were randomised into three groups. Group 1 received one tablet of sulfadoxine-pyrimethamine (SP) (each containing sulfadoxine 500 mg and pyrimethamine 25 mg) twice a week; group 2 received two tablets of sulfadoxine-pyrimethamine (SP) once a week; and group 3 received one tablet of mefloquine (250 mg) and one tablet of sulfadoxine-pyrimethamine (MSP) once a week. Blood films for malaria parasites were examined and body weight, haemoglobin levels, body temperature, and spleen and liver sizes were recorded before and 5 months after the start of the trial. At 5 months blood film positivity rates for malaria parasites were 43·66% for group 1, 70·37% for group 2, and 1·02% for group 3. Only group 3 showed improvement in haemoglobin levels and liver and spleen rates. MSP should thus be used for prophylaxis against multidrug-resistant falciparum malaria, at least in those exposed to life-threatening levels of malaria transmission.