12-Hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in the pathogenesis of inflammatory skin diseases. Recently, high-affinity binding sites for this eicosanoid have been identified on human keratinocytes by our group. Since ciclosporin exerts therapeutic effects in chronic inflammatory dermatoses such as psoriasis or atopic eczema, the influence of the drug on 12(S)-HETE binding to human keratinocytes was studied. No competitive inhibition of 12(S)-HETE binding was observed in ciclosporin concentrations between 10-10 and 10-6M. In contrast, pretreatment of epidermal cells for 24 h resulted in a dose-dependent decrease of specific 12(S)-HETE binding. The analysis of saturation curves showed that the inhibition of 12(S)-HETE binding by ciclosporin was due to the decrease of 12-HETE binding sites, while receptor affinity remained unchanged. In addition, ciclosporin blocked the interferon-γ-induced increase in epidermal 12(S)-HETE binding. These findings suggest that the effects of ciclosporin in cutaneous disorders could be partly mediated via an influence on epidermal 12(S)-HETE binding