We investigated whether serum thyroglobulin (Tg) measured at the time of remnant ablation (ablation-Tg) could be a prognostic indicator complementary to serum Tg levels at the time of the first diagnostic whole-body scan (WBS) after thyroid hormone withdrawal (control-Tg; approximately 6-12 months after ablation-Tg) and whether ablation-Tg could predict the persistence or recurrence of disease in low-risk patients with differentiated thyroid carcinoma. Patients with differentiated thyroid carcinoma (n = 268) treated with total or near-total thyroidectomy followed by immediate (131)I remnant ablation were studied. Patients with anti-Tg autoantibodies and those showing evidence of extracervical metastases were excluded. Two patients showing remnant uptake on follow-up diagnostic WBS received a second ablation. We found significant correlation between ablation-Tg and control-Tg levels; 114 of 143 patients (80%) with ablation-Tg greater than 2 microg/liter showed detectable (>/=1 microg/liter) control-Tg, and 70 of 125 (56%) patients with ablation-Tg 2 microg/liter or less showed undetectable (<1 microg/liter) control-Tg [odds ratio 5.1, 95% confidence interval (CI) 3.0-8.9, P < 0.001]. When the 268 patients were followed up for a mean period of 5.7 +/- 1.4 yr (range 2.8-8.3 yr), 35 (13%) had recurrences; 73 (27%) were classified as "Tg positive, no evidence of disease"; and 160 (60%) showed complete remission. Of 143 patients with ablation-Tg greater than 2 microg/liter, recurrence was observed in 33 cases (23%); "Tg positive, no evidence of disease," was observed in 52 cases (36%); and complete remission was observed in 58 cases (41%). Of 125 patients with ablation-Tg 2 microg/liter or less, two patients (2%) showed recurrence during the follow-up; 21 patients (17%) were regarded as "Tg positive, no evidence of disease"; and 102 patients (81%) showed complete remission. The positive predictive value for recurrence in patients having ablation-Tg greater than 2 microg/liter was found to be 23.1% (33 of 143 patients, 95% CI 16.4-30.8%). The negative predictive value for recurrence in patients having ablation-Tg 2 microg/liter or less was found to be 98.4% (123 of 125 patients, 95% CI 94.4-99.8%). These data indicate that serum Tg levels measured at the time of immediate postoperative (131)I remnant ablation correlated well with serum Tg levels at the time of the initial diagnostic WBS and had a complementary role for predicting persistence or recurrence of disease in the earliest postoperative period.