The serum thyroglobulin (Tg) response to elevated TSH is one of the most sensitive indexes of residual thyroid carcinoma. We have explored the possibility that this test alone would be sufficient to detect residual thyroid carcinoma in thyroid cancer patients after total thyroidectomy and radioiodine remnant ablation. We used recombinant human TSH (rhTSH) to elevate serum TSH, rather than withdraw the patients from thyroid hormone. Routine evaluations, including diagnostic radioiodine whole body scans (DxWBS) and serum Tg, were performed on 366 patients after preparation by rhTSH, over a 2-yr interval. A retrospective analysis of the data from these patients revealed that 76% of those whose stimulated Tg rose to more than 2 microg/liter had evidence for residual thyroid carcinoma, whereas the same was true for only 13% of those whose stimulated Tg was 2 microg/liter or less. Using risk group stratification, we analyzed outcomes in a low risk subset (which excluded patients with elevated Tg levels on suppression, known metastatic disease, and clinical or histological evidence of aggressive disease). In this low risk group, we found that a stimulated Tg of 2 microg/liter or less had a 91.7% negative predictive value. No low risk patient who had had a prior negative DxWBS and a stimulated Tg of 2 microg/liter or less had any evidence of residual thyroid carcinoma. We conclude that the stimulated Tg alone is not sufficient by itself to screen unselected patients, but that it may be sufficient in low risk patients, especially those who have had a prior negative DxWBS.