Thyroidectomy (TX) is no longer the preferred choice for the therapy of hyperthyroid Graves' disease but is an alternative in patients who are noncompliant with or have reactions to antithyroid drugs, have moderate to severe ophthalmopathy, have large goiters, or who refuse (131)I therapy and/or long-term antithyroid drug therapy. Seventeen clinically and biochemically severely thyrotoxic patients (16 female, mean age of 35 yr), all but one with large goiters, underwent TX after rapid preparation. The potent inhibitors of the deiodination of T(4) to T(3), iopanoic acid (IOP) (500 mg twice a day) and dexamethasone (DEX) (1 mg twice a day), were given with propylthiouracil or methimazole, when possible, and beta-blockers. Thyroid function tests were obtained before treatment and at TX. All patients were thyrotoxic (mean +/- SE: T(4), 21.6 +/- 1.2 micro g/dl; free T(4) index (FTI), 10.3 +/- 0.8; total T(3), 510 +/- 48 ng/dl). IOP and DEX rapidly lowered T(3) values (P < 0.0001; total T(3), 147 +/- 13 ng/dl) with a smaller but significant (P < 0.05) decrease in T(4)/FTI (T(4), 17.9 +/- 1.3 micro g/dl; FTI, 7.9 +/- 0.6). All patients were clinically euthyroid before surgery. None developed hypoparathyroidism, laryngeal nerve damage, or worsening of ophthalmopathy after surgery. The restoration of hyperthyroid Graves' disease to euthyroidism is rapidly accomplished with IOP and DEX, beta-blockers, and, when possible, antithyroid drugs. This is especially relevant in noncompliant patients with large goiters.