Abstract NOD.H2h4 mice spontaneously develop autoimmune lymphocytic thyroiditis that mimics human Hashimoto’s thyroiditis, a disease where iodine, IFN-γ, and adhesion molecules have all been implicated in the pathogenesis. To study how iodine and IFN-γ modulate the expression of ICAM-1, we analyzed NOD.H2h4 thyrocytes in baseline conditions (day 0) and at several time points following supplementation of iodine in the drinking water. On day 0, a small percentage (∼10%) of thyrocytes constitutively expressed ICAM-1. The expression gradually increased to 13, 25, and 41% on days 7, 14 and 28, respectively, returning to baseline (9%) on day 35. The initial ICAM-1 kinetics was paralleled by thyroidal infiltration of CD45+ hemopoietic cells, which increased from an average of 4% on day 0 to an average of 13, 21, and 24% on days 14, 28, and 35, respectively. To distinguish whether the observed ICAM-1 increase was a direct effect of iodine or a consequence of the immune infiltrate, we treated mouse primary thyrocyte cultures with 0.01 mM sodium iodine and showed a 3-fold increased ICAM-1 expression. To assess interaction between IFN-γ and iodine, we analyzed CD45 and ICAM-1expression on thyrocytes from NOD.H2h4 wild-type and NOD.H2h4 thyr-IFN-γ transgenic littermates. Strikingly, IFN-γ interacted synergistically with iodine to enhance ICAM-1 expression on thyrocytes. These findings suggest that iodine and IFN-γ cooperate to promote thyroidal expression of ICAM-1 in this mouse model of thyroiditis, highlighting the complex interplay present in the pathogenesis of Hashimoto’s thyroiditis.