Spontaneous autoimmune thyroiditis in obese strain (OS) chickens provides an excellent animal model for the study of Hashimoto's autoimmune thyroiditis in humans. The data presented in this paper indicate that nonspecific esterases (NSE) may play a role in or serve as a marker for the target organ susceptibility. Experiments have shown that follicular epithelial cells and interfollicular macrophages in connective tissue stain positively for NSE as early as the first day after hatching, a time at which infiltrating lymphocytes are not yet observed. We also have observed NSE positivity of follicular cells in the vicinity of mononuclear cell infiltration in all OS chickens, as well as weaker positivity in 6-month-old, avian leukosis virus free, Brown Leghorn outbred chickens, which appears in each case to correlate with infiltration of lymphocytes. In F2 hybrids between OS and healthy CB inbred chickens, the intensity of NSE staining was more variable than in OS chickens. Using specific inhibitors eserine, Na-taurocholat and p-hydroxymercuribenzoic acid, we were able to inhibit in vitro the NSE positivity of thyroid gland follicular epithelium, indicating that this staining was not an artifact. Experiments are currently in progress to clarify the relationship between the presence of NSE in follicular epithelium and the predisposition to spontaneous autoimmune thyroiditis.