The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq 131iodine 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 < or = 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 > or = 75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume < or = 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.(ABSTRACT TRUNCATED AT 250 WORDS)