Tetracyclines are used for prophylaxis of malaria and treatment of drug-resistant falciparum malaria because of their safe drug action. We re-evaluated effects of three tetracyclines against drug-resistant Plasmodium falciparum in vitro. Minocycline was approximately 4 times and twice more potent in inhibiting the in vitro growth of falciparum parasites than tetracycline and doxycycline, respectively. Compared with doxycycline, significant inhibitory effects of minocycline to chloroquine, pyrimethamine and mefloquine resistant P. falciparum strains were affirmed by the present in vitro study. By electron microscopy a number of electron dense vesicles with a single membrane bound were observed in the cytoplasm of minocycline-treated parasites, although no distinct structural alternations of mitochondria was noted. Minocycline may be a better therapeutic drug than doxycycline which is widely accented as the standard antimalarial tetracycline.