Background A wart is a skin lesion caused by infection with human papillomavirus (HPV). Contact immunotherapy is one of the many therapeutic options that have been used to treat warts; however, the effectiveness of contact immunotherapy differs from patient to patient, and the cause of this variation in clinical response is unclear. Aim To assess cytokine changes in patients after contact immunotherapy with squaric acid dibutylester (SADBE). Methods In total, 21 patients with warts and 9 healthy control subjects were enrolled in the study. The frequencies of CD3+ T cells expressing interleukin (IL)-4, IL-10, IL-12, tumour necrosis factor-α and interferon-γ were measured by flow cytometry analysis of peripheral blood at baseline in both patients and controls, and after SADBE treatment in patients. Results Lower expression of IL-4 and higher expression of IL-12 in CD3+ T cells were found in patients compared with controls. The percentage of CD3+/IL-4+ T cells significantly increased after contact immunotherapy in all responders, but was significantly higher in those with an excellent response, who also had a significantly higher percentage of CD3+/IL-10+ T cells. The patients with an excellent response also had a significant decrease in the percentage of CD3+/IL-12+ T cells, and the percentage of CD3+/IL-4+ T cells normalized. Conclusions Response to contact immunotherapy can vary depending on the types of cytokine changes produced by treatment. An excessive shift to a Th2 pattern and increased IL-10 production after contact immunotherapy may hinder clearance of HPV.