Background: Radioiodine ((131)I) is an alternative to surgery for the treatment of multinodular goiter (MNG). Frequently, high activities of (131)I are required for effective thyroid volume reduction OM, due to the low and heterogeneous radioactive iodine uptake (RAIU). Thiamazole (MTZ) may be used as an adjuvant to (131)I, by increasing RAIU. Objective: To evaluate the effects of MTZ in the treatment of MNG with (131)I, in terms of TV reduction. Design/methods: Nine female patients (aged 73.8 +/- 7.4 years) with MNG (eight with subclinical hyperthyroidism) were treated with MTZ. Doses started at 10 - 20 mg, and were adjusted monthly based on thyroid hormone levels. RAIU and TV were measured at baseline, and repeated when TSH levels > 6 mU/l were achieved. At that time, 1.11 GBq of (131)I were administered. Results: Patients were treated with MTZ for 2.8 +/- 0.8 months. When a tracer activity of (131)I was administered, the mean serum TSH was elevated to 11.7 +/- 5.4 mU/l. MTZ led to significant increases in 24-h RAIU, from 21.3 +/- 8.1% to 78.3 +/- 15.3% (p < 0.001). One year after (131)I, median TV decreased from 97 ml (range 47 - 555 ml) to 56 ml (range 13 - 350 ml), a mean reduction of 46.2 +/- 17.8% (p = 0.012). Eight patients (89%) had subclinical hyperthyroidism, which was reversed in all patients after 1 year. Five patients (56%) developed overt hypothyroidism, and no clinical adverse events were observed. Conclusion: Pretreatment with MTZ targeting against an increased serum TSH did not impair the effects of (131)I. In our patients with MNG, MTZ increased RAIU and possibly enhanced (131)I efficacy, leading to significant TV reduction and reversion of hyperthyroidism in all patients.