Malaria, in particular Plasmodium falciparum infections remain a major world health problem. Increasingly, a major concern in malaria control is the emergence and spread of chloroquine resistance. The mechanism of action of chloroquine is still under study. The mechanisms of development and spread of resistance to chloroquine are only speculative. We plan to develop isogeneic clones of chloroquine sensitive and resistant P. falciparum. Phenotypic and karyotypic studies are outlined utilizing these clones to better understand chloroquine resistance at the molecular level. Simultaneously we plan to develop a DNA specific diagnostic probe for chloroquine resistant P. falciparum to be utilized in field surveys. Epidemiologic data from such a probe could be an integral part of malaria control programs. Elucidating the mechanisms of resistance to chloroquine and better definition of the extent of the problem could help in reducing the morbidity and mortality associated with P. falciparum infections.