An American Peace Corps volunteer contracted chloroquine-resistant Plasmodium falciparum malaria while serving in Malawi and taking regular chloroquine prophylaxis. Resistance was confirmed by in vitro testing of his parasites for chloroquine and pyrimethamine. The possibility of Fansidar®-resistant falciparum malaria was also suggested in this case. American expatriates residing in or traveling to Malawi are advised to either take both chloroquine and Fansidar®, or alternatively amodiaquine or doxycycline alone. Any breakthrough of slide-proven falciparum malaria in these individuals should be seriously suspected to be chloroquine- and Fansidar®-resistant malaria, and should be treated with quinine and tetracycline.