The effects of pyronaridine on the morphology of Plasmodium falciparum were studied in an infected owl monkey (Aotus trivirgatus) that was severely ill with a parasitemia of 28%. Thirty minutes after pyronaridine administration, distinct morphologic changes were already present in late trophozoites and schizonts. Ultrastructural observations revealed that the earliest and most distinct changes induced by pyronaridine occurred in food vacuoles. The most striking change in food vacuoles was the appearance of undigested endocytic vesicles surrounded by a single membrane in the vacuolar space. These findings suggest that vacuolar degradation is inhibited by pyronaridine, and that undigested endocytic vesicles accumulate inside parasite food vacuoles impairing hemoglobin degeneration. Thus, pyronaridine appears to interfere with the parasitic digestive system.