A new commercially available chemiluminescent TSH assay demonstrates an 8- to 10-fold increase in sensitivity over a sensitive immunoradiometric assay, allowing increased ability to distinguish partial from more complete thyrotroph suppression. Sera were analyzed from 145 patients who had TSH concentrations below 0.08 mU/L in the immunoradiometric assay. Most patients with overt hyperthyroidism had undetectable TSH concentrations in the chemiluminescent assay. Three groups of patients were identified, in which a large subgroup had undetectable values in the immunoradiometric assay and detectable values in the chemiluminescent assay (12 of 17 patients under treatment for hyperthyroidism who had recently normalized their serum thyroid hormone levels, 33 of 68 patients taking L-T4, and 4 of 8 patients with endogenous subclinical hyperthyroidism). In addition, several patients with undetectable basal and detectable TRH-stimulated TSH values in the immunoradiometric assay had detectable basal TSH values in the chemiluminescent assay. The utility of first generation TSH immunometric assays was their ability to distinguish hyperthyroidism from euthyroidism. The clinical utility of increasingly sensitive TSH assays will be to distinguish degrees of thyrotroph suppression in subclinical hyperthyroidism.