Increasing evidence suggests an important regulatory function for 1 alpha,25-dihydroxyvitamin D3 in the growth control of epidermal cells and in skin immunology. Using immunohistochemical techniques we investigated the in situ expression of 1,25-dihydroxyvitamin D3 receptors (VDR) in normal human skin with one monoclonal rat antibody and four monospecific polyclonal rat antibodies to the VDR. Polyclonal rabbit antibodies have been raised against synthetic peptides corresponding to different amino acid residues of the human VDR, including regions close to the DNA binding domain and the hormone-binding domain. All antibodies revealed positive immunoreactivity in normal human skin. The antibodies showed differences in subcellular immunoreactivity and staining-intensity. Differences in subcellular distribution of VDR immunoreactivity are caused by the different epitopes recognized by the antibodies and not by the affinity of the antibodies for VDR. It seems that the antibodies may recognize different functional modifications of the receptor molecule (i.e.: hormone bound vs. hormone free; DNA bound vs. non-DNA bound; VDR vs. VDR/retinoid-X receptor [RXR] heterodimers). Using these newly raised antibodies future studies will be carried out to analyse subcellular distribution of VDR immunoreactivity in skin pathology.