We report clinical, radiological and virological data from nine consecutive HIV-infected patients with herpes simplex virus (HSV) infection of the central nervous system (CNS). Three patients presented with confusion, two with fever and headache, two with anxiety and depression, one with slow mentation and memory loss and one with expressive dysphasia. Five patients had previous AIDS-defining diagnoses: four of these five patients had previous cutaneous HSV infection. HSV DNA was detected by the polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) in seven patients. HSV infection was diagnosed by brain biopsy (after negative PCR on CSF) in one patient and at autopsy in one patient (after negative CSF PCR and brain biopsy). Seven patients received specific anti-viral therapy; two died of unrelated causes and the other five recovered. Two patients were not treated, in one the diagnosis was made at autopsy and the other recovered spontaneously. HIV-infected patients with CNS HSV infection have a varied presentation. Diagnosis by PCR on CSF identified the majority of cases. With specific treatment the outcome was good.