Leukocyte-associated Ig-like receptor (LAIR) is a small family-receptor able to inhibit immune cell function via collagen binding. It exists as both membrane-bound and soluble forms. LAIR-1 functions as an inhibitory receptor on natural killer cells, T lymphocytes and monocytes. In addition to LAIR-1, the human genome encodes LAIR-2, a soluble homolog. Several studies have focused on LAIR-1, whereas few investigations concentrate on the expression and function of LAIR-2. We demonstrate the presence of high LAIR-2 levels in 74/80 sera from patients with autoimmune thyroid diseases (both Graves' disease and autoimmune thyroiditis). LAIR-2 levels seemed not to be related to specific clinical manifestations, such as thyroid functions (hypo- or hyperthyroidism), or specific clinical features (such as ophtalmopathy). In addition, serum LAIR-2 is able, in vitro, to bind its natural ligand, collagen. Since LAIR-2 has been found to have higher affinity for collagens than LAIR-1 did, we hypothesize a potential regulating capability of serum LAIR-2 in finally regulating the inhibitory capability of LAIR-1.