The aim of this prospective study was to determine the frequency and clinical significance of detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from 120 HIV-infected individuals. Six of 8 CSF samples from patients with recent (up to 8 months previously) or concurrent cutaneous zoster contained detectable VZV DNA using the polymerase chain reaction. No detectable CSF VZV DNA was present in two patients who had an encephalopathy complicating cutaneous zoster or in 112 other patients without a history of recent or concurrent zoster. In conclusion, VZV DNA may be detected in CSF of patients with neurological disease and concurrent or recent zoster. However, the absence of detectable VZV DNA in CSF does not preclude the possibility of VZV associated neurological complications.