Multidrug-resistant falciparum malaria is a major health problem along the Thai-Burmese border. From July 1985 until December 1986 a total of 5192 patients with falciparum malaria (1734 males, 3458 females) from this area were given supervised treatment with the combination mefloquine-sulfadoxine-pyrimethamine (MSP). The radical cure rate, assessed 21 days after drug administration, was 98.4% for the first 1975 patients, and 98.8% when assessed at 28 days for the remaining 3217 patients. In 3.8% of cases, parasites were still detected in peripheral blood smears on day 7 after treatment but this had fallen to 0.27% by day 9. Adverse reactions among the first 1975 patients were: vertigo (7.5% of patients), vomiting (5.8%), epigastric pain (0.6%), and transient confusional state (one case). MSP is an effective and well-tolerated drug for the treatment of drug-resistant falciparum malaria; however, delayed parasite clearance may give a false impression of RII resistance.