The natural history of warts shows considerable variations between individuals, ranging from spontaneous regression to prolonged persistence. The level of cytokines participate in the immune response to human papilloma virus. This work investigates local expression of T-helper1 (Th1)/ T-helper2 (Th2)/ cytokines in a trial to disclose the different immunological mechanisms affecting the natural history of warts. A total of thirty patients suffering from different types (common, plane, plantar and anogenital) of viral warts were included. An excision biopsy was used to assess tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) expression. Local expression of TNF-alpha (Th1) and IL-4 (Th2) in wart tissue was determined using in-situ hybridization technique. The cytokines probes used in this assay detect messenger RNA (mRNA) in wart tissue. Local expression of TNF-alpha mRNA was higher in viral wart patients compared to healthy control (P < 0.01), while local expression of IL-4 was not significantly higher in patients compared to control (P > 0.05). Statistical analysis was done to determine whether variations in cytokine mRNA expression depend on wart location or clinical types. In conclusion, immunoreactivity to warts is likely to be associated with a predominant Th-1 or mixed Th-1/ Th-2 cytokine mRNA expression profile. However, it does not appear to be a simple causal relationship between expression of a Th-1 pattern and clearance.