We have previously reported that stimulation of human fibroblasts (FB) with interferon-gamma (IFN-gamma) leads to their increased adhesiveness for resting peripheral blood T lymphocytes. With the use of blocking monoclonal antibodies, we determined that intercellular adhesion molecule-1 (ICAM-1) and its T cell ligand, lymphocyte function-associated antigen-1 (LFA-1) are the major, if not only ligands involved in this system. Using an ELISA, we have confirmed earlier reported observations that IFN-gamma induces an increase of ICAM-1 expression on the surface of FB suggesting that this increase mediates lymphocyte adhesion. However, we show that treatment of FB with IL-1, while leading to comparable increases in ICAM-1 synthesis and expression, failed to induce increased adhesion. In contrast, treatment of fibroblasts with the phorbol ester, TPA, stimulated ICAM-1-dependent adhesion without an increase in ICAM-1 surface expression. This suggested that the detection of ICAM-1 by monoclonal antibody techniques may not always correlate with its functional capabilities. The contrasting effects of IFN-gamma and IL-1 on ICAM-1-dependent FB adhesion suggest that qualitative as well as quantitative alterations of the ICAM-1 molecule may regulate ligand interaction.