Measurements of serum thyroglobulin (hTg) were performed using a specific radioimmunoassay. Sera with detectable anti-thyroglobulin (anti-Tg) antibody titers (> or = 1:10) as assessed by passive hemagglutination were discarded. Assays were carried out under conditions in which anti-Tg titers less than 1:10 produced no interference. The assay sensitivity was 1.25 ng/ml and the mean +/- SE concentration of serum hTg in 58 control subjects was 9.5 +/- 0.9 ng/ml (range < 1.25-27 ng/ml). A slight but significant (p < 0.025) increase in the mean hTg level was observed in 12 pregnant women at delivery (25.7 +/- 5.2 ng/ml). Moderate to marked elevations of serum hTg were observed in patients with nontoxic goiter (61.4 +/- 15 ng/ml; n = 23), subacute thyroiditis (138 +/- 67 ng/ml; n = 5), toxic adenoma (129 +/- 47 ng/ml; n = 13), untreated (424 +/- 101 ng/ml; n = 35) or treated (328 +/- 222 ng/ml; n = 14) toxic diffuse goiter. 88 patients with thyroid carcinoma and 10 with nonthyroidal malignancies were studied. The mean level of serum hTg was increased in untreated differentiated thyroid carcinoma (89.5 +/- 19 ng/ml; n = 13) but not in undifferentiated (10 +/- 2.9 ng/ml; n = 6) or medullary (0.8 +/- 0.2 ng/ml; = 3) carcinoma. In treated differentiated thyroid carcinoma the mean hTg levels were normal (8.2 +/- 0.2 ng/ml) in patients (n = 24) with no evidence of either a thyroid residue or metastatic disease, moderately increased (56.6 +/- 16 ng/ml) in patients (n = 27) with residual thyroid tissue, markedly elevated in patients with lymph node metastases (199 +/- 50 ng/ml; n = 5) and extremely elevated in those with bone (4004 +/- 982 ng/ml; n = 8) or lung (2520 +/- 620 ng/ml; n = 5) metastases. There was no significant difference in serum hTg between functioning (n = 23) and nonfunctioning (n = 5) metastases as assessed by 131I whole body scan. A slight but significant (p < 0.0005) increase in the mean concentration of hTg was observed in nonthyroidal malignancies (21.7 +/- 4.5 ng/ml; n = 10). Serial measurements showed a transient increase of serum hTg after 131I therapy of differentiated thyroid carcinoma, toxic diffuse goiter or toxic adenoma, with peak values usually occurring within the first three days. A fall of serum hTg after administration of suppressive doses of thyroid hormone to patients with nontoxic goiter and a rise after discontinuation of thyroid suppressive therapy in patients with metastatic differentiated thyroid carcinoma was observed.(ABSTRACT TRUNCATED AT 400 WORDS)