Few studies have suggested that neuropeptide Y (NPY) could play an important role in skin functions.However, the expression of NPY, the related peptides, peptide YY (PYY) and pancreatic polypeptide (PP)and their receptors have not been investigated in human skin. Using specific antisera directed against NPY,PYY, PP and the Y1, Y2, Y4and Y5receptor subtypes, we investigated here the expression of these markers.NPY-like immunoreactivity (ir) in the epidermal skin could not be detected. For the first time we reportthe presence of positive PP-like ir immunofluorescent signals in epidermal cells, i.e. keratinocytes of skinfrom three areas (abdomen, breast and face) obtained as surgical left-overs. The immunofluorescent signalof PP-like ir varies from very low to high level in all three areas. In contrast, PYY-like ir is only expressedin some cells and with varied level of intensity. Furthermore and for the first time we observed specific Y1and Y4receptor-like ir in all epidermal layers, while the Y2and Y5subtypes were absent. Interestingly, asseen in human epidermis, in Episkin, a reconstituted human epidermal layer, we detected the presenceof PP-like as well as Y1-like and Y4-like ir. These data have shown the presence and distribution of PYY,PP and Y1and Y4receptors in the human skin and Episkin, suggesting possible novel roles of NPY relatedpeptides and their receptors in skin homeostasis.