We used an in vitro isotopic drug sensitivity assay to assess the sensitivity of Plasmodium falciparum isolates collected in Bangui, Central African Republic between March and July 2004. We tested antimalarials that are currently in use in this country (chloroquine, amodiaquine, quinine, and pyrimethamine), antimalarials that will become available in this region in the future (artemisinin and halofantrine), and prophylactic antimalarials (mefloquine, doxycycline, and atovaquone). The proportions of resistant isolates were 37% for chloroquine, 15.9% for amodiaquine, 0% for quinine, 0% for dihydroartemisinin, 1.6% for mefloquine, 3.8% for halofantrine, 4.0% for atovaquone, and 38.3% for pyrimethamine. No multi-resistant isolates (showing resistance to more than three drugs) were found. A positive correlation was found between the 50% inhibitory concentrations values for the following drugs: chloroquine and amodiaquine; quinine and halofantrine; chloroquine and dihydroartemisinin; chloroquine and halofantrine; amodiaquine and dihydroartemisinin; dihydroartemisinin and mefloquine; chloroquine and quinine; and quinine and dihydroartemisinin. These findings suggest that the Ministry of Health should recommend a interim policy with the amodiaquine plus sulfadoxine-pyrimethamine combination as the first-line antimalarial drug in Bangui until better alternative treatments such as artemisinin-based combination therapies become available at low prices in the Central African Republic.