The endothelium lining the posterior corneal surface performs physiologic pump functions essential to corneal clarity and integrity. A hallmark of keratitis, anterior ocular inflammation, and corneal allograft rejection is leukocyte adherence to the corneal endothelium (CE) forming keratitic precipitates. To elucidate mechanisms governing cornea-leukocyte interactions, cultured human CE cells and intact corneas were examined for expression of intercellular adhesion molecule-1 (ICAM-1), which binds the lymphocyte function-associated antigen-1 (LFA-1) on all leukocytes and enhances delayed-type hypersensitivity mediated by class II major histocompatibility complex antigens. Immunohistochemistry on culture CE cells using monoclonal anti-ICAM-1 antibody yield positive staining that increased after exposure to interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (gamma-IFN). Standard leukocyte adherence assays demonstrated ICAM-1-mediated CE-neutrophil binding, which was specifically blocked by antibody to ICAM-1 or antibodies to LFA-1 on neutrophils. In whole human corneas, gamma-IFN increased CE and stromal keratocyte ICAM-1 immunoreactivity and enhanced CE-neutrophil adherence. As in CE cell cultures, antibody to ICAM-1 effectively blocked neutrophil binding to the CE cells of whole corneas. These results are the first to demonstrate ICAM-1 in ocular tissue. They indicate that CE cells express functional ICAM-1, which may be modulated by inflammatory cytokines, ICAM-1 provides mechanisms for keratitic precipitate formation, regulation of corneal leukocyte trafficking and the generation of immune responses that may be crucial to allograft rejection.