Plasmodium knowlesi infected rhesus monkeys were employed for investigating brain tissue damage in experimentally induced cerebral malaria. Light microscopic studies revealed parasitic infiltration of virtually all the regions of CNS. Electron microscopic observations confirmed the light microscopic findings. These studies further revealed the presence of macrophages in the blood vessels of infected monkeys. In conclusion, the pathogenesis of cerebral malaria seems to be an outcome of a typical triad consisting of: (1) mechanical obstruction of the blood capillaries by parasitized RBCs; (2) biochemical events, involving free radicals, and (3) immunological dysfunction.