Background: Perforin (Pf), a pore-forming protein, is a cytolytic protein of killer cells. Its deposition in lesioned skin has not been studied. Objective: The purpose of this study is to show Pf deposition in the lesioned skin and Pf expression in the dermal infiltrates of various inflammatory skin diseases. Methods: Frozen specimens obtained from 29 patients with 5 different diseases were immunohistochemically stained. Results: Granular deposition of Pf was found in the lesioned skin in 2 out of 5 cases of viral vesicles and in 3 out of 7 cases of erythema multiforme. In the cases with Pf deposition, the percentages of Pf+ cells in the dermis were higher than in those without deposition. Conclusion: Pf released from natural killer cells or cytotoxic T lymphocytes may play a role in tissue damage.