S-100 protein, isolated from mammalian brain, has widely been used for immunohistochemical marker of the glia cells and the cells derived from the neural crest. In the present study, we made anti S-100 protein antibody and studied the immunoreactive distribution of S-100 protein in the cutaneous nervous system. Albino rabbits were immunized with S-100 protein and complete Freund adjuvant, and antiserum was purified by ion-exchange chromatography. Formalin-fixed normal human skin and sciatic nerve of rat were examined by the PAP method. S-100 protein was detected in Schwann cells of sciatic nerve of rat and cutaneous nerve bundles of human skin specimens. Meissner corpuscles and inner core cells of Pacinian corpuscles of human skin were S-100 protein positive. These findings suggest that the staining of S-100 protein with PAP method is a simple and reliable method to demonstrate the cutaneous nervous system. Also, lamellar cells of Meissner corpuscles and inner core cells of Pacinian corpuscles are indicated to be Schwann cell origin.