PURPOSE: The precise determination of organ mass (mth) and total number of disintegrations within the thyroid gland (Ã) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose-response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves' disease (GD) treatment planning were calculated using different approaches to estimating the mth and the Ã. METHODS: Fifty patients were included in the study. Thyroid (131)I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (Teff) of (131)I in the thyroid; the thyroid cumulated activity was then estimated using the Teff thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA∕EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. RESULTS: The average ratio (± 1 standard deviation) between mth estimated by SCTG and USG was 1.74 (± 0.64) and that between à obtained by Teff and the integration of measured activity in the gland was 1.71 (± 0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when mth was measured by either USG or SCTG and à was determined by the integration of measured (131)I activity in the thyroid gland and based on Teff, respectively. No statistically significant relationship was found between therapeutic response and patients' age, administered (131)I activity (MBq), 24-h thyroid (131)I uptake (%) or Teff (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and mth (p ≤ 0.035). CONCLUSIONS: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient's mth and Ã. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating mth and Ã.