Merkel cells are specialized skin receptor cells, characterized by their particular location in the epidermis and close association with nerve terminals. Although they can be distinguished ultrastructurally by their small, electron-dense secretory granules, there is no specific and reliable method for identifying them by light microscopy. Using antibodies to neuron-specific enolase (NSE), the authors have shown sparsely distributed groups of specifically immunostained cells and associated nerve terminals in the nose skin of cats and rats. These cells were easily distinguished from other epithelial cell types, including melanocytes and Langerhans cells and had all the morphologic features of Merkel celIs and their so-called neurite complexes, including the characteristic cytoplasmic secretory granules (60 nm in diameter). NSE immunostaining is a simple and reliable method for the specific lightmicroscopic staining of Merkel cells and provides further evidence for NSE as a marker for the diffuse neuroendocrine system.