The existence of Langerhans cells in the stratified squamous epithelium of severely combined immunodeficient (SCID) mice was studied by enzyme histochemistry, immunohistochemistry and electron microscopy. Considerable numbers of ATPase-positive Langerhans cell were observed in the epidermis (ear and hind limb) as well as in the stratified squamous mucosal epithelium (forestomach and tongue) of SCID mice. The cells also expressed Ia antigen. This indicates that, in spite of the lack of functional T and B lymphocytes, the antigen-presenting function of Langerhans cell was retained in SCID mice. In the epidermis, frequency of Ia expressing Langerhans cells was low, but in the forestomach epithelium, 90% of Langerhans cells had strong Ia positivity. In the forestomach epithelium of SCID mice, the regulation of Langerhans cell maturation was affected differently from the epidermis. As with normal mice, the occurrence of Langerhans cell in female SCID mice was higher than in males; hormonal immuno-regulations may be normal in SCID mice. Under electron microscopy, many Birbeck granules were observed in epidermal Langerhans cells but few in those of the mucosal epithelium. In SCID mice, Langerhans cell exists constitutively in the epidermis and mucosal epithelium, where the cell may function in a defense system independent from T and B lymphocytes.