Much research into falciparum malaria coma assumes the primary event to be vascular obstruction by parasitized red blood cells. Recent evidence that vivax malaria, caused by a parasite traditionally thought not to block blood flow, seems to alter brain function to the same degree as falciparum malaria has seriously questioned this. These data are a timely call to reassess whether vascular obstruction should still be considered the primary cause of the coma of falciparum disease. They add to a growing literature that suggests that enhancement of brain-origin cytokines, such as tumour necrosis factor, by non-brain systemic inflammation and an appreciation of the degree to which neuronal homeostasis depends on them provide a more fruitful research direction.