The use of 131I for radioablative therapy in patients with differentiated thyroid cancer (DTC) requires a sufficient serum concentration of TSH for efficient thyroid tissue uptake of iodine. We describe the use of recombinant human TSH (rhTSH) in conjunction with ablative radioiodine therapy (RIT) in 11 patients (16 total treatments) with advanced and/or recurrent DTC (5 papillary, 6 follicular) for whom withdrawal of thyroid hormone suppression therapy (THST), the standard method to increase serum TSH, was not an option. Indications for rhTSH use in these patients included inability to tolerate withdrawal of thyroid hormones due to very poor physical condition or inability to achieve sufficient serum TSH levels after THST withdrawal. Ten patients had undergone thyroidectomy, and most (9 of 11) had received prior ablative RIT after THST withdrawal. Baseline thyroglobulin levels ranged from 25 to nearly 30,000 ng/mL, reflecting the heterogeneity of the patient population. In 7 cases (5 patients), posttherapy thyroglobulin levels assessed at a mean of 4.3 months (range, 2-10 months) after 131I therapy were decreased by at least 30% compared to pretherapy levels. In follow-up visits, an additional 3 patients showed marked clinical improvement or decreased or stabilized tumor burden in whole body scans compared to pretherapy scans. Three patients died of progressive disease within 2 months of therapy before follow-up assessments occurred. No adverse events were reported among the 8 surviving patients. The results suggest that rhTSH offers a promising alternative to THST withdrawal to allow ablative RIT after effective TSH stimulation in patients with advanced recurrent DTC who would not otherwise be able to receive this treatment. This therapeutic indication extends the clinical potential of this new agent, already demonstrated to be effective for use with 131I for diagnostic purposes.