Objective: To discuss evidence that immune mechanisms are involved in the pathogenesis of some forms of epilepsy. Data Sources: Computerized data sources and published indexes and articles. Study Selection: Published reports showing disorders of the immune system in patients with epilepsy and in animals with experimental epilepsy. Data Synthesis: Rasmussen encephalitis is an example of an autoimmune disorder of the central nervous system. Serum samples of patients with this disease contain antibodies to the glutamate receptor GluR3, and immunization of animals with GluR3 induces a disorder resembling the human disease. There are still few data to prove that immune mechanisms are involved in the pathogenesis of intractable childhood epilepsies other than Rasmussen encephalitis. Epilepsy is more common in patients with systemic lupus erythematosus who have antiphospholipid antibodies, and it is possible that these antibodies can lead to immune-mediated cortical damage. Immune defects in patients with epilepsy may occur as a consequence of long-term antiepileptic treatment or may represent a genetic coupling to the convulsive disorder. Conclusion: The finding of an immunological basis may offer new modalities for the treatment of selected cases of intractable partial epilepsies.