A prospective study was conducted to evaluate the effect of prolonged treatment of hyperthyroid Graves' disease with methimazole (MMI) for 12 months or Na ipodate for only 6.6 ± 1.1 months, since the drug had to be discontinued because of persistent or recurrent hyperthyroidism during treatment. The eight patients who were treated with MMI alone for 12 months became euthyroid, and seven remained in remission for at least 6 months after MMI was discontinued. In contrast, only two of 10 patients treated with Na ipodate alone became euthyroid and remained so during therapy. Na ipodate was discontinued in the eight patients who did not respond, and they were then treated with MMI. One patient had recurrent hyperthyroidism after NA ipodate was discontinued, and she was then treated with MMI, MMI was efficacious in treating these nine patients, and all patients were euthyroid by the third month of MMI administration. Five of these nine patients remained euthyroid for at least 6 months after MMI was discontinued, a remission rate that was not significantly different from that observed in the eight patients treated only and initially with MMI (Fisher's Exact Test). There was no significant change in serum thyroid peroxidase antibodies during treatment with MMI alone, Na ipodate alone, or Na ipodate followed by MMI. In conclusion, the present study strongly suggests that Na ipodate is not useful in the long-term treatment of Graves' hyperthyroidism since only two patients could be succesfully treated for 12 months, one of whom had a recurrence 6 months later, and that MMI is less efficacious in reducing serum thyroid hormone concentrations following Na ipodate withdrawal due to the iodide load associated with Na ipodate administration. © 1993.