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Purpose: Epilepsy was a well-recognized disease in pre-Columbian cultures. However, anthropological studies about epilepsy in native cultures living at the present time are scarce. The objective of this paper was to study native perception and myths about epilepsy, their magic-religious healing rites and ceremonies, and the natural treatments that archaic cultures used. Methods: An anthropological fieldwork was performed in Central and South America with Tzeltal Maya (Chiapas, Mexico, 1995), Kamayurá (Matto Grosso, Brazil, 1999) and Uru-Chipaya people (Bolivian Andes, 2004). We collected information from shamans and medicine men about epilepsy beliefs and the use of traditional treatments. Results: Epilepsy is called tub tub ikal by Tzeltal people. It is caused by an attack suffered by the animal spirit who accompanies the person, after a fight between the spirits who serve the forces of good and evil. People with chronic epilepsy are considered witches. Epilepsy is called teawarup by Kamayurá, and is caused by the revenge of the spirit ( mama'e) of the armadillo killed by a huntsman. It is treated with two roots, tsimó and wewurú, kneaded and diluted in water. Epilepsy is called tukuri by the Chipaya people, and is originated by a witchcraft that enters into the nose and the head, as a wind. Tukuri is treated with a ritual animal sacrifice called willancha, and by taking several dried insect infusions and bird's blood. Conclusion: These American native cultures have developed a system of orally transmitted knowledge about epilepsy based on magic-religious traditions. [ABSTRACT FROM AUTHOR]