The clinical course of 306 Graves' patients treated with methimazole (MMI) was reviewed with the aim of establishing criteria able to predict remission of hyperthyroidism after medical treatment. One hundred and ninety-four (149 females, 45 males) of 306 (63.4%) patients had relapse of hyperthyroidism after antithyroid drug (ATD) withdrawal. Relapse was more frequent during the first months of the follow-up, but still it was observed 3 years after MMI withdrawal. The relapse rate was dependent on the age of the patient, the size of goiter, and the level of TSH-receptor antibody (TRAb) at diagnosis, being observed in 40 of 47 (85%) patients with high (> 30 U/L) TRAb level and in 54 of 101 (53%) patients with low TRAb level (< or = 30 U/L; p <.0002). Remission was more frequent (43.3%) in patients having the combination goiter size < or = 40 mL, TRAb level < or = 30 U/L, than in patients with goiter size > 40 mL and high TRAb levels (9%). In the subgroup of patients with the combination: goiter < or = 40 mL- TRAb < or = 30 U/L - age at onset > 40 years, the remission rate was 80%, and all relapses occurred within the first 9 months after MMI withdrawal. In conclusion, our study confirms that hyperthyroidism relapses in the majority of patients with Graves' disease treated with ATD. Among different clinical and laboratory features, age at onset of hyperthyroidism, goiter size and TRAb level are particularly helpful in identifying those patients who are more prone to undergo a remission of hyperthyroidism after medical treatment and may be useful to select the minority of Graves' patients who will benefit from antithyroid drug treatment as a first choice.