In 27 patients with a first episode of herpes simplex virus type 2 (HSV-2)-induced meningitis, confirmed by virus isolation from the cerebrospinal fluid (CSF) or seroconversion to HSV-2, initial neurologic complications were found in 10 (37%) but subsided before 6 months in all patients. Long-term complications were recurrent meningitis in 5 (19%) and periodic headache related to genital HSV recrudescences in 4 (15%). Seven additional patients had possible HSV-2-induced recurrent meningitis. In contrast to the first episode of meningitis, virus isolation, HSV antigen detection, and IgG analyses in consecutive serum samples were of no diagnostic value in episodes of HSV-2-induced recurrent meningitis. Instead, immunoblotting was used to assay intrathecally produced IgG antibodies to the HSV-2 type-specific protein gG-2 in recurrent meningitis, when CSF was collected at a minimum of 3 days after onset.