BACKGROUND: Chicken pox is commonly known as a benign exenthamatous disease of childhood, occasionally neurologic or hemorrhagic complications, or even death may ensue. Early predictors of severity of disease have yet to be identified. TNF-alpha and IL-6 stimulate virus-specific immunoglobulin production and it has been postulated that determination of levels of these cytokines may be useful as a prognostic factor. PATIENTS AND METHODS: Patients who were diagnosed with a varicella-zoster virus (VZV) infection in the Outpatient Clinic of the Department of Pediatric Infectious Diseases were evaluated for eligibility. Laboratory assays included an evaluation of complete blood counts, erythrocyte-sedimentation rate (ESR), c reactive protein (CRP), and the number of tumor necrosis factor-alpha/interleukin-6-(TNF-alpha/IL-6-) producing mononuclear cells as determined by flow cytometry. RESULTS: A total of 339 patients (320 with chickenpox and 19 with shingles) were enrolled. Blood samples could only be obtained from 81 of the 320 patients with chickenpox. Patients were also divided into three groups depending on the number of skin (vesicular) lesions. (group 1, ≤ 50 lesions; group 2, 51-100 lesions; group 3, >100 lesions). Correlation analyses did not reveal the presence of a statistically significant correlation between number of skin lesions with either of white blood cells (WBC) count (p = 0.231), ESR (p = 0.879) or CRP (p = 0.373). The mean percentage of TNF-alpha-producing mononuclear cells was significantly higher in group 2 compared to group 3 (p = 0.003). A similar difference was observed with regard to IL-6-producing mononuclear cells, albeit bordering on statistical significance (p = 0.058). CONCLUSIONS: Decreased expression of the cytokines TNF-alpha and IL-6 may be responsible for the development of a more severe clinical picture in patients with VZV infection, and determination of intracellular levels of these cytokines may be of benefit for early identification of patients who may have a more severe clinical course.