Abnormal keratinocyte proliferation and differentiation, the main characteristics of psoriasis, may be induced and maintained by cytokines produced by activated resident and recruited inflammatory cells in lesional skin. As the epidermal cytokine profile is clearly altered in psoriasis and because increased expression of interleukin-4 receptor (IL-4R) has been reported in some epithelial proliferative diseases, we investigated the expression of IL-4R on psoriatic epidermal cells (ECs). The expression of IL-4R on freshly isolated ECs from healthy skin and untreated psoriatic lesions was studied by immunostaining using an IL-4R-specific antibody and by examining their capacity to bind biotinylated recombinant human IL-4 using flow cytometry. The number of IL-4R+ ECs and the number of binding sites per cell were significantly increased on psoriatic ECs as compared with healthy control ECs. Immunostaining confirmed these results, whereby staining was mainly observed in the lower epidermal layers. In addition, an increased IL-4R mRNA expression was also observed in psoriatic epidermis using a digoxigenin-labeled IL-4R RNA probe. In short-term in vitro cultures, lipopolysaccharide/phorbol-myristate-acetate-stimulated and unstimulated psoriatic ECs did not produce any immunoreactive IL-4. The results of this study together with the reported increased expression of IL-4R in epithelial neoplasias suggest an association between overexpression of IL-4R and abnormal keratinocyte activation and proliferation.