Mediators of lymphocyte infiltration in inflammatory thyroid disease have yet to be identified. Here we examine the ability of IL-1 and other proinflammatory cytokines to enhance the production of chemoattractants by human thyrocytes. Primary cultures, when treated with the cytokine, release T lymphocyte chemotactic activity. The effect of IL-1 is time-dependent and the chemoattraction activity can be partially attenuated by the addition of either anti-IL-16 or anti-RANTES neutralizing antibodies. IL-16 is a CD4⁺-specific ligand and RANTES is a C-C type chemokine that targets monocytes and lymphocytes. These chemoattractants could be detected by specific ELISAs in conditioned medium from IL-1 treated thyrocytes. Northern analysis revealed that thyrocytes express high constitutive levels of IL-16 mRNA which were invariant with regard to IL-1 (10ng/ml) or glucocorticoid treatment. RANTES mRNA was not detected in control cultures but was strongly induced by the cytokine. IL-16 but not RANTES expression was dependent on the activity of caspase-3. Pro-IL-16 protein could be detected in homogenates of thyroid tissue from patients with multinodular goiter and Graves' disease. Thus, human thyrocytes, through the expression of chemoattractants, may participate in the recruitment of lymphocytes to the thyroid in inflammatory states.