Background: Radioactive iodine (RAI) therapy and whole-body scanning are the fundamentals of treatment and follow-up of patients with differentiated thyroid cancer. It is generally accepted that a Thyroid-Stimulating Hormone (TSH) level of at least 30 μU/ml is a prerequisite for the effective use of RAI, and that it requires 4-6 weeks of off-thyroxine to attain these levels. Because thyroxine withdrawal and the consequent hypothyroidism are often poorly tolerated, and occasionally might be hazardous, it is important to be certain that these assumptions are correct. We have measured serial changes in serum TSH after total thyroidectomy or withdrawl of thyroxine in patients with thyroid cancer. Subjects and Methods: Serum TSH levels were measured weekly after thyroidectomy in 10 patients (group A) and after the discontinuation of thyroxine in 12 patients (group B). Symptoms and signs of hypothyroidism were also evaluated weekly by modified Billewicz diagnostic index. Results: By the second week, 78% of group A patients and 17% of group B patients had serum TSH levels ≥ 30 μU/ml. By the third week, 89% of group A patients and 90% of group B patients had serum TSH levels ≥ 30 μU/ml. By the fourth week, all patients in two groups achieved target TSH levels and there were no overt hypothyroidism. Conclusion: In all patients, serum TSH elevated to the target concentration (≥30 μU/ml) within 4 weeks without significant manifestation of hypothyroidism. The schedule of RAI administration could be adjusted to fit the needs and circumstances of individual patients with a shorter preparation period than the conventional.(Korean J Nucl Med 38(6):516-521, 2004)