Purpose: The expression of cellular adhesion molecules in 31 penetrating keratoplasty specimens from a broad range of corneal inflammatory diseases was studied using monoclonal antibodies and an immunoperoxidase technique. Methods: Corneas were divided into noninflamed, mild to moderately inflamed, and severely inflamed groups based on histologic findings. The panel of adhesion molecules studied included HLA-ABC, HLA-DR, CD3, LFA-1, MAC-1, ICAM-1, PECAM-1, VCAM1, and E-selectin-1. Results: The adhesion molecules ICAM-1, HLA-DR, PECAM-1, CD3, VCAM-1, LFA-1, and MAC-1 were selectively expressed in areas of corneal inflammation. In general, HLA-DR and intercellular adhesion molecule ICAM-1 were co-expressed in similar regions. PECAM-1 was restricted to zones of marked inflammation and vascularization. E-selectin-1 was detected only in the stroma of a graft melt in a patient with active ocular cicatricial pemphigoid, and may reflect a primary regulatory dysfunction in this disorder. The ICAM-1 ligand was, in general, more diffusely distributed than its receptor LFA-1, a beta-2 integrin found on leukocyte cell membranes. The localization of the integrin MAC-1, present on macrophages, neutrophils, and some lymphocytes, did not always parallel the staining pattern of ICAM-1, suggesting promiscuity in its binding to other ligands besides ICAM-1. Conclusions: Adhesion molecules are detected readily at sites of corneal inflammation and may play a critical role in facilitating the recruitment of immune regulatory cells to these areas. Future efforts to block or modulate the expression of intercellular adhesion molecules may provide new therapeutic options in the treatment of corneal inflammatory diseases.