Febrile seizures (FS) are common and are associated with increased probability of temporal lobe epilepsy (TLE). However, whether FS can provoke TLE in the nonpredisposed brain is unknown. Using an immature rat model, we established that long FS cause TLE, and that duration of FS governed the severity of epilepsy. Epileptogenesis was accompanied, perhaps causally, by ion channel dysfunction and inflammatory changes. Because FS are a prevalent antecedent of TLE, studying the epileptogenesis that follows them provides powerful insight and potential therapies for epilepsy. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AC, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at). © 2010 International League Against Epilepsy.