Intercellular adhesion molecule-1 (ICAM-1) and class II major histocompatibility complex antigens (MHC II, HLA-DR), are two cell-surface ligands known to be critical to the initiation and propagation of immune-mediated inflammation. Their expression in tissue is induced by proinflammatory mediators, principally interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. We examined human orbital fibroblasts and intact human orbital tissue exposed to these mediators for the presence of immunoreactive ICAM-1 and HLA-DR antigen. These ligands were detectable on stimulated fibroblasts and on fibroblasts and vascular endothelium in samples of orbital fat and muscle. ICAM-1 reactivity was diffuse and occurred in response to all three proinflammatory mediators. In contrast, HLA-DR reactivity was intense but limited to fewer numbers of cells. Our results, demonstrating the differential expression of these two ligands, may help further to elucidate the underlying pathogenetic mechanisms involved in the initiation and perpetuation of immune-mediated orbital inflammatory diseases.