Human intercellular adhesion molecule-1 (ICAM-1) is a cell-surface glycoprotein that serves as one of the major ligands for lymphocyte function-associated antigen-1 (LFA-1), a member of the integrin supergene family of adhesion molecules that is involved in cell-cell adhesion. Homotypic and heterotypic conjugate formation between leukocytes and between leukocytes and target cells via the LFA-1/ICAM-1 interaction has been demonstrated to be a critical event in numerous immunologic and inflammatory processes. While LFA-1 is expressed by all leukocytes, ICAM-1 is not normally expressed by all tissues with which leukocytes interact, but ICAM-1 may be induced de novo by various cytokines, including interferon-gamma (IFN-gamma). The constitutive and IFN-gamma-induced expression and function of ICAM-1 in human keratinocytes (HK) and A-431 cells in culture has been analyzed. While A-431 cells constitutively express ICAM-1 when assessed by northern blotting, by biosynthetic labeling and immunoprecipitation, and by flow cytometry, HK do not. When these two cell types are exposed to recombinant human (rh-) IFN-gamma at 1000 U/ml for 24 h, A-431 cells upregulate ICAM-1 and HK express ICAM-1 to an equal degree when assessed by these same parameters. Furthermore, in an in vitro adhesion assay, rh-IFN-gamma treatment of the HK or A-431 cells greatly increases the specific adherence of radiolabeled T cells to these cells. These data provide further evidence for the potential role of the regulated expression of ICAM-1 by keratinocytes in immunologic and inflammatory responses occurring in the skin.