We report that the mitotic inhibitor, vinblastine (VLB), is highly toxic to the malarial parasite, Plasmodium falciparum. In cultures in vitro growth is inhibited by 50% at a VLB level of about 28 nM, and totally abolished at a level of 100 nM. By tests on synchronized cultures we have found that the effect of VLB takes place at the trophozoite stage. Colcemid also inhibits schizogony with somewhat different kinetics. By mutagenesis with nitrosoguanidine followed by VLB selection we have isolated a VLB-resistant mutant which exhibits cross-resistance to vincristine. These data suggest a critical role of microtubules in the asexual schizogonic cycle of P. falciparum.