The effect of antithyroid drugs on the efficacy of radioiodine ((131)I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of (131)I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive (131)I alone (32 patients) or (131)I plus pretreatment with methimazole (30 mg/d; 29 patients). (131)I was administered 4 d after drug discontinuation. The calculated (131)I dose was 200 mu Ci/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T(4), and free T(4) were measured 4 d before (131)I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning (131)I treatment. After I yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and Ts levels (P = 0.002). Multiple logistic regression analysis identified T(3) values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of (131)I therapy.