Mesial temporal sclerosis (MTS) is a common pathologic finding in patients with temporal lobe epilepsy. Rarely MTS can be detected in children during the first decade of life, but is not commonly found until adolescence. Although the etiology of MTS remains controversial, there is now a considerable amount of evidence demonstrating that MTS is both a result and a cause of seizures. Clinical studies suggest that prolonged seizures or complicated febrile seizures may result in MTS. A variety of epileptogenic agents administered to adult animals have resulted in MTS and spontaneous recurrent seizures. The mechanism of the lesions is due to excessive excitability secondary to release of excitatory amino acids, primarily glutamate. Glutamate, acting at a number of subreceptors on the postsynaptic membrane, leads to prolonged depolarization of neurons and results in the entry of cytotoxic amounts of calcium. Interestingly, the same agents that produce MTS in adult animals do not produce MTS in immature animals. Clinical and experimental evidence suggests that although prolonged seizures or complicated febrile seizures can place a child at risk for MTS, a period of time is required for the lesions to develop fully.