Varicella-zoster virus (VZV) reactivation can lead to the development of neurological disease. Diagnosis has been based on the detection of VZV DNA in cerebrospinal fluid (CSF) by PCR-based methods. The aim of this study was to determine whether the VZV DNA copy number in the CSF correlates with the course of the disease and to determine its prognostic relevance. VZV DNA was quantified in CSF samples obtained from 30 patients with neurological disease due to VZV reactivation using real time PCR, and the VZV DNA copy number was correlated to the clinical and laboratory findings for each case. Viral loads ranged from 50 copies/ml to 2.6 x 10(8) copies/ml. Significantly higher viral loads [geometric mean (GM): 7.2 x 10(4) copies/ml] were found in patients with encephalitis compared to patients with meningitis (GM: 4.1 x 10(3) copies/ml) (P=0.01, Mann-Whitney U test). In eight patients without zoster dermal lesions no significant difference in viral load (GM: 4.6 x 10(3)) was detected compared to patients exhibiting dermal lesions (GM: 2.2 x 10(4)) (P=0.14). High copy numbers of VZV DNA in CSF were clearly associated with the severity of neurological disease and none of the patients with a VZV viral load below 10(4) copies had a disease course which required intensive care.