The combination of halofantrine and primaquine therapies was calculated as a regimen for achieving radical curve of falciparum or vivax malaria in Irian Jaya, Indonesia, and compared with combined chloroquine and primaquine therapies. The patients who volunteered for the study [adult, male, Indonesian immigrants with no previous exposure to endemic malaria, normal glucose-6-phosphate dehydrogenase (G6PD) activity, uncomplicated malaria illness, no prior use of antimalarials, and parasitaemias of 0.001%-1.1%] were randomized to receive either halofantrine (24 mg base/kg bodyweight, in three equal doses over 12 h) or chloroquine (25 mg base/kg bodyweight over 48 h, in doses of 10, 10 and 5 mg base/kg at 24-h intervals). Each patient also received concurrent daily primaquine (0.5 mg base/kg bodyweight) for 14 days followed by the same dose on alternate days to day 28. A recurrent parasitaemia during the 28 days of follow-up constituted drug failure. Of the 40 cases of falciparum malaria and 26 cases of vivax malaria treated with halofantrine-primaquine, none had a recurrent parasitaemia (100% efficacy). In contrast, 20 of 30 patients with falciparum malaria and three of 27 with vivax malaria had recurrent parasitaemias after chloroquine-primaquine, giving efficacies of 33% and 89%, respectively. Halofantrine-primaquine was significantly more effective than chloroquine-primaquine against falciparum malaria (P < 0.001) but was similarly efficacious against vivax malaria (P = 0.23). On average, fever associated with falciparum or vivax malaria cleared 17 h faster with halofantrine-primaquine (P < 0.01) although there were no significant differences (P > 0.4) in parasite-clearance times between the two regimens. The halofantrine-primaquine regimen was also associated with a more rapid and significant decline in malaria-related physical complaints.