Previous studies of Ammon's horn sclerosis (AHS) suggest that AHS is both the result of and the cause of seizures, and support the idea that seizures cause alterations in cell numbers and location. To test the hypothesis that epilepsy induces neurogenesis/gliogenesis, hippocampal cell proliferation was assessed in AHS. Twelve and four resected hippocampi in patients with AHS and with tumor-related epilepsy (TRE), respectively, and 11 autopsy controls were immunostained for Ki-67. Total number of Ki-67-positive cells (KiPC) in each hippocampal area was counted. Selected cases were further studied with double immunohistochemical labeling. KiPC were observed in all three groups. Total numbers of KiPC were significantly higher in AHS cases than in controls, but were not significantly different between TRE cases and controls. Significant differences were observed in the dentate gyrus, the cornu ammonis (CA)-4 region, and the fissura hippocampi between the AHS and control groups. In double immunolabeling, nestin was positive in some KiPC. The existence of neurogenesis/gliogenesis was shown in the hippocampi of pediatric patients with AHS. Increased numbers of progenitor cells in the hippocampi with AHS appear not to be due to seizures per se, but to be more associated with the specific cause of epilepsy.