BACKGROUND Cell adhesion molecules are cell surface proteins that allow specific cell-cell interactions among leukocytes, as well as between leukocytes and other cells. Because middle ear cholesteatoma is characterized by the presence of leukocyte infiltrates, the presence of the two molecule types of intercellular adhesion molecules (ICAM-1 and ICAM-2) was investigated on cholesteatoma using monoclonal antibodies. METHODS Tissue sections from 10 patients with cholesteatoma, and normal skin from 5 patients were prepared for alkaline-phosphatase--anti-alkaline-phosphatase (APAAP) staining. RESULTS ICAM-1 and ICAM-2 were present in normal skin in microvascular endothelial cells and in intersticial cells of the dermis. Cholesteatoma showed a very important increase of the ICAM-1 expression with comparison to human skin. All infiltrating immune cells showed positive reactions for the antibody. Furthermore, the intensity of the staining of vessels cells was higher than in normal skin. Keratinocytes were only positive if a very heavy infiltrate was present subepidermally. ICAM-2 was present in endothelial and intersticial cells in normal skin and in cholesteatoma. Most of the infiltrating cells in the cholesteatoma stroma showed positive reactions for the anti-ICAM-2 antibody. CONCLUSIONS Our results suggest that both ICAM-1 and ICAM-2 play a central role in the regulation of the inflammatory disorders observed in cholesteatoma.