We prepared a mouse monoclonal antibody that racts specifically to human Langerhans cells (LC). The protein recognized by this antibody was mainly in the membranes of Birbeck granules and realted structures. Using this anti-body, we could identify LC in various tissues; these cells were in the skin, stratified squamous mucosal epithelia, lymph nodes, and the thymus. The antibody did not react with monocytes, tissue macrophages, lymphoid dendritic cells, follicular dendritic cells, or interdigitating cells. The antigen purified with this antibody was a heterogenously glycosylated protein of M, ˜ 40,000 without interchain disulfide bonds. This antibody may be useful for identifying LC in various human tissues with or whithout abnormalities, and for studying the origin and fate of Birbeck granules of LC.