Treatment of hyperthyroidism with sodium iodide I 131 has been implicated as a stimulus to long-acting thyroid stimulator (LATS) production and ophthalmopathy. To evaluate this postulate, we reviewed data of 484 thyrotoxic patients treated with this drug. The incidences of hypothyroidism at one, five, and eight years were 31%, 44%, and 54%, respectively. Of 94 patients with ophthalmopathy, only 19 showed exacerbation unrelated to posttherapy thyroid function after treatment with sodium iodide I 131. In the serum of 25 of 60 patients, LATS was detected, but no evidence of131I-induced LATS formation was seen six weeks to 30 months after treatment. However, elevated antithyroid-antibody titers were noted within six months of treatment, particularly in patients in whom hypothyroidism was developing. There was no correlation between LATS and ophthalmopathy or between LATS and antithyroid antibodies. These data indicate that LATS formation does not result from thyroid injury, but suggest that hypothyroidism which develops after treatment with sodium iodide I 131 is a manifestation of thyroid autoimmune disease.