Forty-two newly diagnosed patients with Graves' hyperthyroidism were randomly assigned to receive 131I therapy after pretreatment with methimazole (21) or beta-blocker alone (21) and prospectively evaluated, to determine possible effects of methimazole on 131I treatment outcome. After randomization, 8 patients were excluded from the study (5 from pretreatment group and 3 from nonpretreatment group). Radioactive iodine (baseline dose 15 mCi, adjusted for goiter size and/or 131I uptake) was administered after pretreatment with methimazole (30 mg initial dose for at least 2 months and stopped 6 days before treatment) and beta-blocker or pretreatment with beta-blocker alone (atenolol 50-100 mg/d). All but one patient in each group became hypothyroid. A similar length of time was required by both groups to achieve hypothyroidism (112 days, [95% confidence interval [CI] = 28 to 196 days) in the pretreated group and 106 days, [95% CI = 45 to 167 days] in nonpretreated patients). Free thyroxine (T4) normalized 44 +/- 39 days after therapy in the nonpretreated group and 35 +/- 30 days in the pretreated group (p = 0.57) and decreased to subnormal levels 80 +/- 70 days in nonpretreated and 65 +/- 32 days in pretreated patients (p = 0.46). We conclude that pretreating patients with methimazole before radioactive iodine therapy does not interfere with the final outcome. Similar cure rates and time required to achieve hypothyroidism after radioiodine were observed when patients were pretreated with methimazole compared to nonpretreated patients.