Ninety-three hyperthyroid patients were treated with 1 dose of iodine-131 (131I) during the past 10 years. Thirty-three were pretreated with propylthiouracil (PTU), 22 with methimazole (MMI), and 38 received no antithyroid drugs (ATD). ATD were discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months before therapy in one fourth of the cases. The frequency of cures in the 3 groups, 6-8 months after radioiodine therapy, was retrospectively studied. The cure rate among those who discontinued PTU for 5-55 days before 131I was significantly reduced (24%), compared with those who discontinued MMI for the same duration (61%) or those who received no ATD (66%). When PTU was discontinued for more than 4 months, the cure rate was similar to those who received no ATD. It is concluded that if ATD are used as initial therapy for hyperthyroidism, then PTU (but not MMI) may reduce the therapeutic efficacy of subsequent 131I. The reduction in cure rate was observed even when PTU was discontinued for as long as 55 days before 131I therapy. To our knowledge, this is the first report to compare, in one study, the effects of pretreatment with PTU and MMI on 131I therapy.