Management of herpes simplex virus encephalitis (HSE) has been considerably improved by the development of rapid polymerase chain reaction (PCR) assays and by the use of intravenous acyclovir. However, an absence of early antiviral treatment has been associated to a poor outcome in patients with HSE. In the present report, we described the case of a 53 years-old adult immunompetent patient who was admitted to the emergency department of university medical center of Reims (France). At the time of hospitalisation, he was suffering from a febrile encephalitis syndrome evolving for more than 24 hours. A cerebrospinal fluid (CSF) puncture was performed demonstrating the presence of a lymphocytic meningitidis (42 leukocytes/mm3 which 90% of mononuclear cells; CSF protein = 1650 mg/L) associated with high levels of interferon alpha (75 UI/mL). Specific herpesvirus PCR and hybridisation assays (Herpes Consensus Hybridowell, Argene, France) were positive for the detection of HSV-1 genome on this CSF sample. Despite the intravenous acyclovir treatment (15 mg/kg/8 hours) delivered at the time of hospitalisation, this immunocompetent adult patient will dead 15 days later by a cardiorespiratory failure that was related to extensive HSE lesions. The time delay between the beginning of the clinical syndrome and the instauration of intravenous acyclovir treatment (more than 24 hours) was the only point susceptible to explain the presence of extensive CNS lesions in this patient. Specific Herpesvirus PCR detection assays are powerful tools that are actually used to establish a rapid etiological diagnosis of viral meningo-encephalitis. However, in patients demonstrating clinical signs of encephalitis associated with an aseptic CSF, it remains essential to urgently initiate a presumptive intravenous acyclovir treatment (10-15 mg/kg/8 hours). Actually, this medical practice is the only one susceptible to reduce the morbi-mortality rates linked to HSE.