Increasing evidence suggests that the retinoid-X receptors RXR(-alpha,-beta,-gamma) play a crucial part in regulating the transcriptional activity of several steroid hormone receptors, including 1,25-dihydroxyvitamin D-3 receptors (VDR) and retinoic acid receptors (RAR-alpha,-beta,-gamma). We developed a new technique for immunohistochemical in situ detection of RXR receptors, and investigated the localization of RXR-alpha in normal and psoriatic human skin using a recently raised corresponding specific antibody. RXR-alpha positive cells related to the skin were phenotyped by sequential sections and a double-labelling procedure for the simultaneous demonstration of this nuclear receptor and cell membrane antigens, as well as cytokeratin 10, HLA-DR and vimentin. Our findings indicate that: (i) RXR-alpha is strongly expressed in normal and psoriatic human skin; (ii) most of the cell types in normal human skin, including keratinocytes, melanocytes, fibroblasts and skin immune cells such as Langerhans cells, reveal strong nuclear immunoreactivity for RXR-alpha, with less cytoplasmic staining; (iii) altered levels or distribution of RXR-alpha in the skin do not appear to be involved in the genesis of psoriasis vulgaris, but subepidermal and subcellular distribution suggest a function of RXR-alpha in the transition from proliferation to differentiation in epidermal keratinocytes; (iv) expression in the hair follicle points to a contribution from RXR-alpha to hair growth.