Two infants developed unilateral hippocampal swelling on magnetic resonance imaging after prolonged seizures of temporal origin. Subsequent images suggested hippocampal sclerosis. The first child had febrile status epilepticus with exanthem subitum and developed refractory complex partial seizures. Histological findings after temporal lobectomy confirmed hippocampal sclerosis but also revealed sequelae of a focal encephalitis and microdysgenesis of the hippocampus. The second child had signs of brain dysgenesis, but acquired hippocampal damage affecting each side successively was documented by serial magnetic resonance imaging. These cases illustrate that different clinical conditions combining preexisting and acquired pathological characteristics can lead to hippocampal sclerosis.