This study reports on the clinical profiles of herpes simplex encephalitis (HSE) case-patients and the management of acyclovir prescriptions. We designed a study on the causes of encephalitis in France in 2007. Case-patients fulfilling the inclusion criteria were enrolled in all the hospitals that volunteered to participate. Fifty-five of 253 enrolled case-patients were diagnosed with HSE. Three (5%) HSE patients died and 48 (89%) were discharged with persistent neurological symptoms. All HSE patients were prescribed acyclovir, 10 of whom had a 2-week course; 42 a 3-week course; two received incomplete courses; and one received two courses of 21 days each due to relapse. The acyclovir dosage was reported for 45 adult HSE patients, 25 (53%) of whom received 10 mg/kg t.i.d. and 22 (47%) received 15 mg/kg t.i.d. The mortality rate was low despite 49% of patients being admitted to intensive-care units. A high dose of acyclovir was not associated with a better outcome in HSE patients. Most patients had persisting symptoms on discharge suggesting neuropsychological rehabilitation is an important issue for survivors.