Cogan’s syndrome is a rare clinical entity characterized by non-infectious interstitial keratitis with vestibuloauditory dysfunction. The clinical course is extremely variable. In the majority of patients, there appears to be an underlying systemic process, often a “vasculitis”. We were able to study for the first time a sural nerve biopsy of a 38-year-old female with clinically suggested Cogan’s syndrome associated with a severe multiplex type of neuropathy. There were unusual cells in or below the perineurium and along perineurial extensions into the endoneurium which were usually associated with blood vessels and which have thus far not been described in association with any type of peripheral neuropathy. The unusual cells were identified as perineurial cells because (1) they were frequently associated with the perineurium and its endoneurial extensions; (2) they were immunoreactive for antibodies against epithelial membrane antigen (EMA) but did not react with antibodies against protein S100, GFAP, and CD 68; and (3) they showed focally accumulated pinocytotic vesicles and hemidesmosomes. Some of these cells were clearly immunoreactive with antibodies against collagen VI. Electron microscopic examination revealed numerous intracellular bundles of collagen fibers which were surrounded by an amorphous basal lamina-like material, indicating that they were located within intracellular projections of the surface membrane. The number of myelinated and unmyelinated nerve fibers was severely reduced corresponding to the clinical manifestation of the neuropathy and to the atrophy, especially of the distal arm and leg muscles. It is concluded that the changes were caused by a special type of autoimmune reaction involving blood vessels and perineurial cells of peripheral nerves.