This study investigated whether transplantation of fetal raphe tissue into genetically epilepsy-prone rats (GEPR-3s) would reduce the severity of seizures previously exacerbated by depletion of brain serotonin. Mild-seizure GEPR-3s were depleted of brain serotonin by 5,7-dihydroxytryptamine (DHT) and evaluated for seizure severity. Rats then received 15-day fetal raphe tissue, fetal neocortical tissue or were sham grafted. GEPR-3s treated with 5,7-DHT showed increased seizure severity following depletion of serotonin and subsequent reductions in severity as a result of fetal raphe transplantation. Sham- or neocortex-grafted rats maintained elevated seizure severity scores throughout the study. Prominent raphe or cortical grafts were observed within the third ventricle of GEPRs at autopsy. These findings show that transplantation of fetal raphe tissue promotes lasting reductions in increased seizure severity resulting from depletion of serotonin in the GEPR brain.