Focal meningoencephalitis is commonly caused by Herpes simplex virus infection, which typically affects temporal or frontal lobes, and carries a mortality rate of 70% if untreated. On rare occasions, however, the infection is restricted to the brain stem. Polymerase chain reaction analysis of cerebrospinal fluid is the gold standard for the diagnosis of herpes simplex encephalitis. A 46-year-old male was admitted to the hospital with a three-day history of headache and fever up to 39 degrees C. Cerebrospinal fluid findings were in accordance with aseptic meningitis. On the third hospital day, the patient presented with double vision followed by confusion, and gaze paresis developed. The condition rapidly progressed from stupor to coma. A second examination of cerebrospinal fluid revealed a low glucose level (1.2 mmol/l) and cefotaxime with ampicillin were started empirically. All cerebrospinal fluid specimens were negative for bacteria and fungi. Serum IgG antibodies for herpes simplex virus type 1 were found with no intrathecal specific antibody synthesis. A polymerase chain reaction analysis of cerebrospinal fluid sample performed on the seventh day of his illness was negative for herpes simplex virus 1 and 2. A computer tomography scan of the brain did not show any abnormality. Despite antimicrobial and supportive intensive care, the condition of the patient progressively deteriorated and he died on the 11th day after admission. An autopsy revealed hemorrhagic and necrotic brainstem meningoencephalitis, and herpes simplex virus type 1 infection was confirmed by hybridization in situ. Herpes simplex virus encephalitis carries a mortality rate of 70% if untreated. The atypical location of the infection, as well as an atypical clinical manifestation with negative radiological and microbiological tests, could be the reasons for false diagnoses and mistreatment. Many authors advocate the use of empiric acyclovir in any patients with unexplained encephalopathy, since delay in treatment may greatly affect outcome. We describe a patient who died due to a herpes simplex virus 1 encephalitis affecting the brainstem, where nucleic acids were found post mortem by in situ hybridization. On rare occasions, the herpes simplex viral infection, as well as clinical manifestations and pathological changes, is restricted solely to the brainstem.