Thyroiditis occurs in about 50% of diabetic Bio Breeding/Worcester (BBAV) rats. In order to investigate the earliest stages of lymphocyte homing to the thyroid gland in the development of experimental autoimmune thyroiditis, we measured the amount of trapping of peripheral blood lymphocytes (PBL) from BBAV rats to the thyroid gland of syngeneic recipient animals. PBL, from donor normal or diabetic BBAV rats, labelled with 5lCr, were injected, i.v., into normal,“potentially diabetic”or diabetic BBAV recipients. After 24 hr the rats were sacrificed and the radioactivity of selected individual organs counted. Results were calculated as % binding of 5lCr-labelled PBL/unit weight of tissue and expressed as a binding index by comparing to binding to recipient blood lymphocytes. A significant binding index was taken as>1.0. PBL from diabetic or normal donor BBAV rats were shown to bind significantly to the thyroid gland of 8 out of 19“potentially diabetic”or diabetic recipient syngeneic rats, but to none of the normal (non diabetic) recipients tested. Sixty percent of“potentially diabetic”BBAV rats and 50% of diabetic rats at 3-4 months of age showed a significant level of binding of donor lymphocytes from syngeneic diabetic or normal animals to their thyroid gland, while, at 5-6 months the proportion of recipient rats giving positive tests was much less (17%). The source of the donor lymphocytes (diabetic, or normal) did not significantly influence the binding. Lymphocyte binding to pancreas was not significantly greater than to control tissues. These data suggest that target specific binding of lymphocytes to the thyroid gland my be detected early (at 3-4 months) in those BBAV rats which will subsequently develop diabetes and that the abnormality resides in the thyroid gland rather than the circulating lymphocytes. The findings support the idea that there may be a“homing”receptor on the thyroid cell, accounting for the initial lymphocyte infiltration in this organ, of diabetic BBAV rats which later develop thyroiditis.