The efficacy of the combination of a single oral dose of 500 mg artemisinin with a single 500 mg oral dose of mefloquine (AM) in the treatment of uncomplicated falciparum malaria was compared to mefloquine therapy alone (M) in a double-'blind' randomized study in an endemic area in the south of Viet Nam where single low dose treatment was employed and where mefloquine had been recently introduced. 231 patients, 117 AM and 114 M, were studied. Failure of therapy occurred in 1 AM patient and in 3 M patients. The radical cure rate was 84% for the AM regimen and 65% for the M regimen (P = 0.002). Recrudescence (including an unknown percentage of reinfections) occurred in 15% of AM patients and in 30% of M patients (P = 0.01). The mean parasite clearance time was 40 h (SD = 16) for AM and 60 h (SD = 27) for the M regimen (P = 0.0001). No effect of artemisinin was noted on gametocytes present on admission, but new gametocytes developed less frequently in the AM group. The addition of a single dose of 500 mg artemisinin to 500 mg mefloquine increased the efficacy and reduced the rate of recrudescence, but this regimen was not adequate and, for short course regimens, more doses of artemisinin as well as higher, doses of mefloquine should be studied.