Abstract Interleukin-18 (IL-18) is a novel cytokine that plays an important role in the T-helper 1 (Th1) response, primarily via its ability to induce IFN-γ production in T cells and NK cells. Human keratinocytes produce IL-18, as do monocytes and macrophages, which are the two major sources of this molecule. It is thought that IL-18 derived from keratinocytes might be involved in the cutaneous Th1-type immune response. In the present study, we investigated the expression of IL-18 in psoriatic lesional skin and attempted to determine whether immunoreactive IL-18 in crude extracts of psoriatic scales is processed to the mature, active form. Immunohistochemical and RT-PCR analysis showed that the expression of IL-18 was increased in psoriatic lesional skin relative to that in normal skin. Western blotting and an ELISA for IL-18 in combination demonstrated that the immunoreactive IL-18 in extracts of psoriatic scales contained the mature form of IL-18, but most of the IL-18 was pro-IL-18. No bioactivity of IL-18 or IFN-γ inducibility in human PBMC could be detected in psoriatic scales. Taken together, these findings indicate that keratinocyte-derived IL-18 participates in the development of the Th1 response in psoriatic lesions, and that its bioactivity appears to be tightly regulated in cutaneous inflammation.