Thyroglobulin (Tg) levels (ng/ml) were measured in the sera of 51 healthy volunteers (range: 0 to 20), 116 unselected blood donors (0 to 50) and 431 patients under thyrotropin suppression therapy for differentiated thyroid carcinoma. Among these 431 patients, 133 had undergone total thyroidectomy: 107 were in remission (mean +/- standard error of the mean = 0.84 +/- 2.29) and 26 had a recurrence (1974 +/- 586); 298 had undergone unilateral thyroid lobectomy: 292 were in remission (4.65 +/- 12.79) and 6 had a recurrence (1003 +/- 673 range: 18 to 12,000). The degree of thyrotropin suppression had no effect on serum Tg levels, but these were significantly increased by the presence of anti-Tg antibodies. Moderately elevated but stable Tg levels were observed without detectable recurrence during a follow-up period of at least 5 years. Tg was frankly elevated in 4 patients with overt post-lobectomy recurrence (range: 77 to 5,200). A rise, even moderate, of Tg levels after lobectomy is suggestive of a recurrence if it progresses regularly as time goes on (n = 2). It is concluded that in the absence of anti-Tg antibodies Tg assays should be included in the follow-up of patients with differentiated thyroid carcinoma under thyrotropin suppression therapy after unilateral thyroidectomy.