To further understand the mechanism of lymphocyte accumulation within the thyroid gland in autoimmune thyroid disease we have examined the expression, regulation, and functional significance of the intercellular adhesion molecule-1 (ICAM-1, CD54) in human thyroid monolayer cells and immortalized thyroid cell clones. Human thyroid monolayer cells derived from both normal and abnormal human thyroid tissue showed low basal expression of the ICAM-1 antigen by flow cytometric assessment (mean % +/- SD positive cells = 13.7 +/- 6.1) compatible with the presence of ICAM-1 positive nonthyroid cells within the monolayer cultures. However, thyroid cell ICAM-1 antigen expression was further induced by exposure to recombinant human interferon-gamma (IF-gamma). At 100 U/ml, IF-gamma induced ICAM-1 expression in 56.0 +/- 19.0% of thyroid monolayer cells. Even greater expression of ICAM-1 antigen was induced by IF-gamma in human fetal thyroid cell monolayers of high purity (up to 80% of ICAM-1 positivity) thyroid monolayers established from a patient with Graves' disease (up to 84%), and in two immortalized human thyroid cell clones, 12S and TAD-2 (up to 61%). Furthermore, dose-response curves for ICAM-1 and HLA-DR antigen induction by increasing concentrations of IF-gamma showed that ICAM-1 antigen gene induction was 10-fold more responsive to IF-gamma than the HLA-DR antigen gene. In order to explore the functional consequence of ICAM-1 antigen expression by thyroid epithelial cells we examined the binding of peripheral blood mononuclear cells to thyroid monolayer cells and immortalized thyroid cells. These studies revealed a preferential adhesion of human PBMC to IF-gamma-treated thyroid monolayers compared to untreated control monolayer cells. Furthermore, this IF-gamma-induced cell adhesion was specifically inhibited by monoclonal anti-ICAM-1. These experiments demonstrate not only the capacity of human thyroid epithelial cells to express ICAM-1 antigen in the presence of a cytokine but, in addition, identify ICAM-1 antigen as responsible for enhanced T cell binding to thyroid epithelial cells. ICAM-1 antigen may, therefore, play an important role in T cell targeting and accumulation within the thyroid gland in autoimmune thyroid disease.