The level of thyroglobulin in plasma was measured in 904 subjects with a history of head and neck irradiation during childhood to evaluate its potential value in screening for and differentiating thyroid neoplasms. Mean plasma thyroglobulin level was significantly elevated in subjects with nodular thyroid disease versus those without evidence of nodules (49.8 versus 27.0 ng/ml). However, the overlap with normal subjects does not allow thyroglobulin assays to serve as the only screening procedure. The mean levels in subjects with benign and malignant thyroid nodules were indistinguishable (48.8 versus 53.9 ng/ml). Thirteen percent of otherwise normal-appearing subjects had elevated values that may represent clinically inapparent thyroid disease. It is concluded that in screening large numbers of persons at risk for thyroid neoplasia, thyroglobulin assays are useful in combination with other modes of evaluation. The assay is without value in distinguishing benign from malignant disease.