Some authors recently suggested a significant increase in the target dose of radioiodine treatment in Graves' disease. The aim of the present study was to investigate the impact of thyroid gland mass on the success rate of radioiodine treatment. For this purpose, the thyroid function of 105 consecutive Graves' patients was assessed 6 and 12 months after a 131I treatment and correlated to the gland mass. The patients were categorized according to the gland mass into small (< or = 30 g; 19 patients), medium size (31-50 g; 40 patients), and large size (> 50 g; 46 patients) groups (S, M, L groups, respectively). None of the patients received more than a 10,000-rad (100-Gy) target dose. During the calculation of administered 131I activity, late uptake measurement has also been routinely used, in addition to the usual maximal uptake parameter. The established effective half-life of 131I was highly variable (5 +/- 1.2 days; range: 2-7.6 days) and could not be predicted based on other clinical data without measuring an extended radioiodine uptake curve of the given patient. However, the correlation between the administered activity calculated from the complete set of uptake values and that of only a single late one was excellent (r = 0.99). Six months after the 131I treatment, hyperthyroidism was cured in 81% of patients with small and medium size thyroid glands, with 62% euthyroid and 19% hypothyroid ratios respectively. In the early phase of study for large goiters, the same linear mass activity function was used during calculation as in smaller glands. In these 17 patients the nonhyperthyroid result was comparable to the results of treatment of the small and medium size gland groups only after 1 year (77%), but the 6-month success rate was significantly lower (53%; p < 0.05). After obtaining these results, the usual 7000-rad target dose was increased to 8000-10,000 rad (depending on the gland mass) in another group of 29 patients with large thyroid glands that result in an acceptable 6-month success rate of 72%. In conclusion, instead of the "mCi 131I/g gland mass/maximal uptake" dose calculation, we suggest a method in which (1) the late 131I uptake measurement is taken into account and (2) for large goiters there is an additional dose adjustment, ie, increase is needed over the usual linear, size driven calculation. No overall increase of target dose over 10,000 rad is necessary if no antithyroid medication is given shortly before 131I treatment.