Five monoclonal antibodies (MAbs) directed against antigenic domains on thyroglobulin (Tg) not recognized by most anti-Tg human autoantibodies (aAbs) have been used to develop an improved IRMA for serum Tg with a limit of detection of 0.2 micrograms/L. Samples are incubated for 3 h in tubes coated with four anti-Tg MAbs. After washing, the tubes are incubated with the tracer MAb for 20 h at room temperature. Dilution and reproducibility tests demonstrated assay reliability. Tests performed on samples with (n = 361) or without (n = 283) aAbs showed that the TG IRMA Pasteur is largely independent of the marked interference generally caused by aAbs. These results were confirmed with an extended population of 2759 samples. For a cutoff of 1 micrograms/L, sensitivity and specificity were 0.97 and 1, respectively, in a follow-up of differentiated thyroid carcinoma in patients treated by total thyroidectomy.