Merkel cells are a rare cell type located at or near the basal lamina of oral epithelia and epidermis. They are associated with nerves, and may function as touch receptors. Merkel cells are difficult to identify by routine light microscopy, but have been identified by electron microscopy and specific antibodies. We demonstrate here that Merkel cells can be identified by immunohistochemistry, using a monoclonal antibody (LK2H11, Lloyd and Wilson, 1983) to neuroendocrine granules, and a monoclonal antibody (35 beta H11, Gown and Vogel, 1982) to a 54-kD keratin generally located in simple epithelia but not in stratified epithelia. Human oral tissue was fixed in Carnoy's fixative, and adjacent serial sections were stained with the two antibodies. Individual positively-stained cells were generally located at the bases of rete ridges. Cells in the same position in adjacent sections stained with both antibodies. Essentially all cells (94%) staining for neuroendocrine granules also gave a positive reaction for the 54-kD keratin, evidence that a single Merkel cell contains neuroendocrine granules and the 54-kD keratin. Staining of epithelial sheets of human oral tissues revealed a linear distribution of Merkel cells along the bases of rete ridges. We concluded that antibodies to simple epithelial keratins and neuroendocrine granules may be excellent immunohistochemical markers for Merkel cells, thus facilitating future studies to examine changes in Merkel cells and their distribution in pathologic conditions. The observation that Merkel cells can be stained with an antikeratin antibody strongly supports the epithelial origin of these cells.