We report a case of human herpes virus-6 (HHV-6) infection complicated by acute necrotizing encephalopathy (ANE). A 1-year and 3-month-old girl presented generalized seizure following high fever. She was intubated and sedated because of prolonged seizure. Her brain CT scan was normal and cerebrospinal fluid showed albuminocytologic dissociation. She admitted to our hospital due to sustained coma and coagulopathy. On the 2nd day after admission, MRI was obtained. Posterior aspect of bilateral basal ganglia, bilateral thalami, posterior limbs of internal capsule, pons and cerebellar white matter showed hyperintensity on T2-weighted images. On the 3rd day, papula was noticed mainly on the body surface. We examined serological tests and blood polymerase chain reaction study was positive for HHV-6. She was diagnosed as having acute necrotizing encephalopathy and was intensively treated with high-dose methylpredonisolone, high-dose gamma-globulin and barbiturate, however she died on the 14th day. ANE was designated on the basis of accumulated clinicopathological data in our country in 1995. Etiology and pathogenesis of ANE remain mostly unknown. Some viral infections cause ANE, and its prognosis is very poor. Neuroradiological findings are important and typical. In our case, the cause of ANE was thought HHV-6 infection. We should treat carefully HHV-6 infection even though the disease is common in childhood.