Encephalitis by herpes simplex virus (HSV) is an sporadic and the most important cause of encephalitis in the western world. The aim of this study was to describe the main clinical features and response to therapy in a representative serie of cases. Fifteen cases confirmed by polymerase chain reaction were identified in two universitary hospitals in Santiago. Average age was 41 years (range 5-78) being 80% over 30 years old. Most cases presented with fever and sensorial involvement (80%) or headache (67%) and only a minority with seizures or focal signs (£15%). Extracerebral herpetic lesions were present in two patients (13%). Average length of symptoms was 3. 8 days and most cases were associated to type 1 HSV (86.7%). Changes were detected in 91.7% of those evaluated with electroencephalogram, in 81.8% of those evaluated with nuclear magnetic resonance and in only 13.3% of those evaluated with a cerebral CT-scan. All patients were treated with acyclovir and case-fatality ratio was 13.3%, although one death in a patient with AIDS and CNS lymphoma could not be related to HSV. Six patients (40%) showed neurological deficit at discharge. Death or neurological deficit at discharge was associated with a delay > 3 days before acyclovir therapy. (p = 0.01, two-tailed Fisher test)