Encephalitis and other neurologic complications, including acute necrotizing encephalopathy, are associated with human herpesvirus-6 infection. Antiviral treatment against human herpesvirus-6 infection is indicated only for immunocompromised patients. We describe a 15-month-old immunocompetent child with severe human herpesvirus-6-induced encephalitis. The primary infection was characterized by human herpesvirus-6 DNA in cerebrospinal fluid and serum, the presence of serum human herpesvirus-6 immunoglobulin M antibodies, and a rise in serum human herpesvirus-6 immunoglobulin G antibodies. Magnetic resonance imaging demonstrated multiple, partly symmetric, necrotic lesions in the pons, medulla oblongata, thalamus, external capsules, and occipital subcortical and cortical areas. High-dose ganciclovir (18 mg/kg/day) was used as antiviral treatment, without side effects. A pharmacokinetic analysis of ganciclovir was performed. The initial recovery from severe disease was good. At 3-year follow-up, neurologic sequelae included epilepsy and ataxia. This case suggests that treatment with ganciclovir should be considered in human herpesvirus-6 central nervous system infections because the neurologic sequelae may otherwise be severe. Controlled, prospective, clinical trials are warranted, to analyze the pharmacokinetics of ganciclovir in infants.