A simple solid-phase radiometric assay for the measurement of thyroglobulin autoantibodies (TgRA) was developed and evaluated. The assay is semiquantitative, and the results were expressed as a ratio between sample versus negative control (normal human serum). In 59 normal subjects, the mean ratio was 0.93 +/- (SD) 0.34. Thyroglobulin antibodies by radiometric assay, by hemagglutination (TgHA), as well as microsomal antibodies by hemagglutination (MCHA) were measured in 41 patients with a histopathologic diagnosis of Hashimoto's thyroiditis (n = 22), adenomatous goiter (n = 10), carcinoma (n = 5), adenoma (n = 4), and in 59 patients without histopathologic diagnosis of thyroid disease. In patients with Hashimoto's thyroiditis, TgRA, TgHA, and MCHA were positive in 54, 31, and 81% of patients, respectively. 1 patient had positive TgRA with negative MCHA levels, and 2 had negative antibody titers by all methods. Thyrotropin-stimulating hormone levels were elevated (greater than 10 microU/ml) in 17 of these patients. Our results suggest that although the TgRA method is more sensitive than TgHA for detecting thyroglobulin antibodies, its diagnostic sensitivity is not equal to that of MCHA.