The pro-inflammatory properties of interleukin-8 (IL-8) suggest a major role of this peptide in inflammatory processes of skin and other organs. Both biochemical and immunohistochemical studies from our group have demonstrated IL-8 peptide within psoriatic scales and epidermis. So far, however, the relevance of circulating IL-8 and its relation to locally produced IL-8 in this disease remain unclear. Serum IL-8 levels of psoriatic patients were determined in sandwich-ELISA prior to therapy as well as during therapy. Using either the assay from our laboratory or three commercial ELISAs, no correlation was found between serum IL-8 levels and disease severity at any stage of the disease. Similarly, epidermal IL-8-immunoreactivity was monitored immunohistochemically in sequential biopsies from individual psoriatic lesions as they resolved during the course of therapy. Initially, decreased epidermal IL-8 immunoreactivity shifted to a homogeneous staining comparable to normal or non-diseased skin as lesions resolved under treatment. These results indicate a role of IL-8 at local level in psoriatic skin. In contrast to hyperinflammatory diseases like sepsis, where increased serum IL-8 levels are found, in psoriasis either circulating IL-8 is absent or potent mechanisms are operative effectively binding and/or inactivating IL-8 as it enters circulation.