Radioiodine uptake by thyroid remnants and metastases postthyroidectomy for thyroid cancer is increased by withdrawing thyroid hormone, which raises TSH levels. The minimal withdrawal time for maximal uptake is unknown. Therefore, we performed 33 studies in 27 patients after 2 weeks and again after 4 weeks of T3 withdrawal. We examined cervical (or pulmonary) uptake and whole body scanning at 48 h and whole body retention at 48, 72, and 96 h after radioiodine. In 4 studies, only physiological nonthyroidal activity was seen on both scans. Cervical uptake was low in these 4 studies. Of the remaining 29 studies with thyroid activity on both scans, 4 had high cervical uptakes after 2 weeks, which decreased by 4 weeks to less than 50% of the 2 week value. The same trend was seen in whole body retentions. In 2 studies, the uptake increased at 4 weeks compared to that at 2 weeks, but the change was small and was reflected in whole body retention of only 1 of these subjects. In 23 studies, including 6 with metastatic disease, the individual uptakes and whole body retentions were similar after 2 and 4 weeks. The mean uptakes and retentions also did not differ despite significantly higher (P less than 0.001) TSH values at 4 weeks. All definite areas of localization of radioactivity seen on the scans after 4 weeks were seen after 2 weeks. Therefore, radioiodine uptake, scanning, and therapy should be performed after 2 weeks of T3 withdrawal when patients are minimally hypothyroid. Serum TSH should also be measured to identify the rare individual not responding to brief T3 withdrawal.