OBJECTIVE The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroidism led us to perform a study in order to compare a fixed dose regime comprising doses of 185, 370 or 555 MBq based on gland size assessment by palpation only, with a calculated I-131 dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour I-131 uptake determination. DESIGN Prospective randomized study. PATIENTS Two hundred and twenty-one consecutive I-131 treatment. Four hyperthyroid patients referred for patients who died for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remaining 163 patients (143 women) were studied, divided into subgroups according to the type of gland. They all received antithyroid drugs prior to I-131 treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS Thyroid function variables were determined approximately 2 weeks before I-131 treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to I-131 therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of I-131 was carried out. Thyroid volume was also estimated 12 months after I-131 therapy in 78 of the 163 patients. Twelve months after the initial I-131 dose patients could be classified as euthyroid, hyperthyroid or hypothyroid. RESULTS Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthyroid. Seven of 78 (9%) in the calculated dose group and 6 out of 85 (7%, NS) in the fixed dose group were classified as permanently hypothyroid. Finally, 39 of 78 (50%) in the calculated dose group and 49 of 85 (58%, NS) in the fixed 131 group were euthyroid at 12 months after I treatment. One year after I-131 therapy thyroid volume was reduced from 59.3 +/- 9.2 (mean +/- SEM) to 36.2 +/- 6.6 ml (average reduction 39%) in the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6+/-6.1 to 41.17+/-4.7ml (average reduction 32%) (P < 0.001). CONCLUSIONS A semiquantitative approach is probably as good as the more elaborately calculated radioiodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.