Ultrastructural changes to P. falciparum-infected red blood cells were examined in vitro after treatment with antimalarial drugs. Artesunate had the most rapid parasitocidal effect. All three drugs caused structural changes within the parasite, including dilatation of the parasitophorus vacuole membrane, depletion of ribosomes, mitochondrial swelling, and decreased formation of hemozoin crystals. The structure of surface knobs and Maurer's clefts were similar to controls but reduced in number. Only depletion of free ribosomes correlated with antimalarial drug exposure. Drug treatment decreased movement of hemozoin granules within parasites on real-time microscopy, before recognizable morphological changes of parasite death.