Twelve children with type 1 herpes simplex encephalitis (3 with relapse, 9 without) have been monitored during the past 7 years. Ten of the children received intravenous infusion of acyclovir (30 mg/kg/day) for 10 days, 1 child who experienced relapse received 15 mg/kg/day, and another relapsed child received no antiviral agents until relapse. Relapse occurred 20-36 days after initial onset. All relapsed patients underwent another 10 days of acyclovir treatment (30 mg/kg/day). Choreoathetosis appeared as the initial sign of relapse followed by rapidly progressive unresponsiveness in all 3 relapsed patients: in 1 nonrelapsed patient choreoathetosis occurred during the recovery period. In these 4 patients involuntary movement was remitted within 3 months to 2 years. One patient with choreoathetosis died of measles pneumonia 4 months after onset of herpes simplex encephalitis and the surviving 3 were severely retarded. Although neuroimaging sparing of basal ganglia does not indicate structural and functional abnormalities, the disturbance of the neural connection among the basal ganglia and the cerebral cortex, which manifested severe damage over frontal, temporal, and parietal mantles on CT, may be the source of movement disorders in these patients. We conclude that choreoathetosis may be the first sign of relapse of herpes simplex encephalitis in children and may be an indicator of poor prognosis. The neuropathogenesis of choreoathetosis requires further investigation.