Radioiodine (131I) treatment is often applied for the treatment of Graves' disease (GD). The optimal dose of 131I for Graves' hyperthyroidism is debated. Various techniques suggest either fixed doses or varying doses based on elaborate calculations of the gland size, 131I uptake, and 131I turnover. Fixed dose regimens avoid dose calculations but there is no consensus on the actual dose to be administered. We compared two routinely recommended fixed 131I doses of 185 and 370 MBq for this purpose. Fifty nine patients with GD who had not been previously treated with 131I were randomized in two groups. Group A consisted of 33 patients who were treated with 185 MBq of 131I. Group B consisted of 26 patients who were treated with 370 MBq of 131I. Group A patients were 21% male and 78% female, mean age 38.1+/-14.4, range 15 to 77 y. Group B patients were 27% male and 73% female, mean age 40.7+/-11.7, range 27 to 72 y. All patients were reexamined every six months for two years. The following clinical outcomes were noticed: a) Persistent hyperthyroidism, which was considered as failure to treatment, requiring further 131I treatment. b) Hypothyroidism; requiring life-long replacement treatment. c) Euthyroid state. Euthyroid and hypothyroid states were considered as a response to treatment of hyperthyroidism. In Group A, 10 patients (30.3%) became euthyroid and 6 (18.2%) hypothyroid (an overall response of 48.5%), while 17 (51.5%) remained hyperthyroid by the end of the follow-up period. In Group B, 10 patients (38%) became euthyroid and 13 (50%) hypothyroid, an overall response of 88.5%. Non responders were 3 patients (11.5%). No correlation was noted between the outcome of treatment and age, sex, size of the thyroid gland or thyroid uptake in each Group of patients, while a significant correlation was noted between the disease outcome and the amount of administered 131I (P<0.003). The incidence of hypothyroidism by the end of two years of follow up was less in Group A than in Group B and the incidence of non responders to treatment was lower in Group A. In view of the higher cost of treatment, the longer time elapsing to treatment, the number of office visits by the patients and the higher number of patients with persistent hyperthyroidism in Group A, we conclude that a fixed dose of 131I of 370 MBq is more useful and effective for the treatment of GD as compared to 185 MBq of 131I.