To provide a conceptual basis applicable to future antimalarial efforts, we sought to identify the sources of success in three notable campaigns that were consummated largely before DDT became available. A variety of measures directed against the aquatic stages of the anopheline vectors provided the main strategy for the antimalarial programs in Palestine/Israel, Italy, and the Tennessee River Valley of the United States. Source reduction-the modification or elimination of aquatic habitats to reduce mosquito breeding-was applied extensively and proved decisive. In all three regions, transmission of malaria was reduced to the point of extinction. Effective measures against anopheline larvae, in particular through source reduction, depend upon locally derived ecologic concepts that can be adapted to each vector species and applied continuously without limit of time. An integrated control program based on the long-term application of such measures can suppress transmission of malaria in edemic areas, as well as contain episodes of locally increased transmission of malaria.