New approaches are developed from the immunological point of view to elucidate the pathogenesis and pathophysiology of cholesteatoma of the middle ear. Langerhans' cells(LCs) have been known to be antigen-presenting cells in the skin. The authors used an immunohistochemical method to verify the distribution of the LCs in cholesteatomatous tissues and the existence of a few other immunologically active cells, using avidin-biotin-peroxidase technique for cholesteatomatous tissue and external ear canal skin, samples of which were taken from 21 patients during operation. The distribution of LCs among all epithelial cells and in subepithelial tissue were significantly higher in cholesteatomatous tissue. These results showed that active immunological processes including the recruitment of LCs were present in the cholesteatomatous tissue and the activity of these cells might be different from that of the external ear canal skin. It was also suggested that LCs and lymphocytes should play important roles in maintaining chronic inflammatory reaction in the natural course of cholesteatoma and the process of bone destruction.