The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq (131)iodine vs. an activity calculated to deliver 100 Gy for treatment of Graves' thyrotoxicosis. Therapeutic success was defined as the elimination of hyperthyroidism 6 months after radioiodine application (range 4.5-8 months). A success rate of more than 90% in eliminating hyperthyroidism was reported for both approaches, but only in retrospective investigations. Investigated prospectively, hyperthyroidism was eliminated in only 71% of the patients receiving standard activity (70/98) and 58% of those randomized for calculated activity (62/107). In the patients with standard activity, therapeutic success was inversely related to thyroid size. The rate was 100% for thyroid volumes less than or equal to 15 mL, 95% for 16-30 mL, 68% for 31-45 mL, 44% for 46-50 mL, 20% for 61-75 mL and 25% for greater than or equal to 75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume less than or equal to 15 mL) this size/outcome dependency was almost compensated. The rates were 86%, 65%, 45%, 61%, 41% and 45%, respectively. Furthermore, detailed statistical analysis revealed a strong correlation between the success of therapy and the radiation dose actually absorbed by the thyroid. The rate was 11% for a target dose of 50 Gy, 50% for 100 Gy, 67% for 150 Gy, 80 % for 200 Gy, 84 % for 250 Gy, 88 % for 300 Gy, 90 % for 350 Gy and 93% for 400 Gy. Based on the results obtained in the present study, we strongly recommend individual calculation of the (131)iodine activity to be administered for treatment of Graves' hyperthyroidism. However, the target dose should be in the range of 200 Gy.