Serum thyroglobulin (hTg) measurements by commercial radioimmunoassay were performed in the follow-up of 118 patients with differentiated thyroid carcinoma undergoing I-131 local and whole-body scans following surgery and I-131 therapy. Patients with positive anti-hTg antibodies (23% of cases) were excluded. In all remaining I-131 accumulating residual, recurrent, or metastatic tumors, hTg levels were elevated (greater than 6.25 ng/ml, minimum detectable value). Twelve patients with neither recurrence nor metastases had elevated hTg levels. Sensitivity and specificity depended on the threshold used for elevate d hTg levels. At an hTg-threshold of 6.25 ng/ml sensitivity has 100%, specificity has 82%. As hTg levels were reported to depend on endogenous TSH stimulation, it is not yet advisable to replace I-131 scans totally by hTg determination. After having determined an hTg "baseline" below detectable values (less than 6.25 ng/ml), we reduced the number of I-131 scans by half. However, elevated hTg levels were an indication for an I-131 scan. Therefore, on the basis of 23% of our patients who had anti-hTg antibodies the need exists to develop a commercial assay which is independent from antibodies.