We reviewed the clinical and demographic characteristics and outcomes for 13 immunocompromised patients with herpes simplex virus (HSV)-induced meningitis. Eleven patients were receiving chemotherapy for leukemia or lymphoma, and 10 had acquired immunodeficiency syndrome. Patients presented with acute febrile meningitis. The median white blood cell count at the onset of symptoms was 400 cells/mm3. Examination of cerebrospinal fluid (CSF) specimens showed lymphocytic meningitis, but activated lymphocytes and low glucose levels were both noted in 7 patients. HSV DNA was detected in all CSF specimens, and HSV type 2 was identified in 7. Eight patients had suspected HSV-associated mucocutaneous lesions at the time of meningitis onset. Six patients had initial radiculalgia, with sphincter involvement in 2. Eleven patients received intravenous antiviral therapy, but treatment was delayed for 6 patients. Two of the 6 patients for whom treatment was delayed developed encephalitis and died, whereas 2 others experienced persistent neurological symptoms. HSV-2 can cause severe meningitis in immunocompromised patients. Early recognition and treatment might improve the outcome of such infections.