The response of Plasmodium falciparum malaria to antimalarial drugs, mainly chloroquine, the first-line drug of choice for the treatment of malaria in Zimbabwe is reported here for the period 1984-96. Earlier studies (1982-83) had shown that Zimbabwe was free from drug-resistant falciparum malaria. The first chloroquine-resistant cases of malaria were reported in 1984 in the Zambezi Valley in the north-east of Zimbabwe. Following this report several cases of chloroquine resistance have been reported throughout the malaria-endemic regions of the country thus prompting the Ministry of Health to develop a sustainable national surveillance strategy to monitor, on an annual basis, the spread and extent of P. falciparum resistance to antimalarial drugs available to the National Malaria Control Programme (NMCP). Of all the antimalarial drugs assessed in vivo, only chloroquine and halofantrine have shown resistance, while no resistance in vivo was observed for sulfadoxine-pyrimethamine (Fansidar), quinine and mefloquine. The study shows the need to replace chloroquine with alternative antimalarial drugs in areas where chloroquine resistance is high, and an increase in the drug pool against malaria is also recommended considering that all the alternative antimalarial drugs available to the NMCP have faced resistance in various parts of the world.