Synaptophysin (SY), a specific component of the membrane of presynaptic vesicles, has been reported as a novel marker for neurons, certain neuroendocrine cells and their neoplasms including neuroendocrine carcinomas of the skin. The origin of the Merkel cells (MC) being far from clear, this study was performed to establish if normal MC express SY. It is demonstrated by immunofluorescence and immunoelectron microscopy using a monoclonal antibody SY38 to this glycoprotein that normal MC in man, rabbit and pigs express an SY-like reactivity. Although immunoblotting identification of the immunoreactive material gave negative results, it is likely that normal MC contain SY. By immunoelectron microscopy, the staining was located at the surface of cytoplasmic vesicles. In view of the possible involvement of SY in the Ca2+-dependent neurotransmitter release, the observation of an SY-like immunoreactivity in MC supports the view that they are epithelial neuroendocrine cells and that they may possess a neurosecretory function.