We evaluated clinical usefulness of thyroid microsomal antibody (MCAb) and thyroglobulin antibody (TGAb) measured by new sensitive radioimmunoassays (RIA). These assays are simple and reproducible; the intra- and inter-assay coefficients of variation were 3.6-6.8% and 6.6-13.2% in the MCAb assay, and 3.2-7.7% and 7.6-12.3% in the TGAb assay, respectively. In 126 patients with Hashimoto's disease, the antibody activity determined by this RIA correlated with that determined by the hemagglutination assay (HA)(r=0.848 for MCAb, r=0.686 for TGAb, p<0.001). MCAb was detected by RIA in all of 115 HA-positive and 4 of 11 HA-negative patients, and TGAb by RIA in all of 84 HA-positive and 29 of 42 HA-negative patients; the prevalence of MCAb was 94% and that of TGAb was 90% in the disease. Moreover, some showed high antibody activity only in RIA. In another group of 14 patients with biopsy-proved Hashimoto's disease with no antibody activity by routine HA tests, serum MCAb was detected in 3 (21%), TGAb in 11 (79%), and both activities in 2 (14%). Our results indicate that (1) the RIA tests are more sensitive than the conventional HA test, and that (2) the present RIA test for TGAb is more sensitive than that for MCAb in detecting autoimmune abnormalities, especially inpatients with biopsy-proved Hashimoto's disease who give negative results in the HA test.