Serum thyroglobulin levels were obtained in 86 patients who had undergone thyroidectomy and I-131 ablation for differentiated thyroid cancer, and who were receiving or had recently discontinued thyroid hormone suppression therapy. Excellent correlation was observed between serum thyroglobulin levels in patients receiving thyroid hormone suppression therapy and I-131 imaging studies. Serum thyroglobulin levels equal to or below 20 ng/ml indicate the absence of thyroid carcinoma, and values exceeding 60 ng/ml were indicative of active thyroid cancer but may include some patients without clinical evidence of disease. Intermediate serum thyroglobulin levels were observed in a small number of patients with postsurgical thyroid remnants or active disease. Serum thyroglobulin levels are of considerable value in monitoring the activity of thyroid cancer in patients who are receiving thyroid hormone suppression therapy.