Background: Several ubiquitous polyhalogenated compounds (PHCs) have been shown to alter thyroid function in animal and in vitro studies. So far, epidemiologic studies have focused on the potential effect of a small number of them, namely, polychlorinated biphenyls (PCBs) and some organochlorines (OCs), without paying attention to other important PHCs. Objectives: We investigated the relationship between exposure to several PHCs and thyroid hormone homeostasis in Inuit adults from Nunavik. Methods: We measured thyroid parameters [thyroid-stimulating-hormone (TSH), free thyroxine (fT4), total triiodothyronine (tT3), and thyroxine-binding globulin (TBG)] and concentrations of 41 contaminants, including PCBs and their metabolites, organochlorine pesticides (OCPs), polybrominateddiphenyl ethers (PBDEs), perfluorooctanesulfonate (PFOS), and a measure of dioxinlike compounds, detected in plasma samples from Inuit adults (n = 623). Results: We found negative associations between tT3 concentrations and levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites of PCBs (MeSO2-PCBs), and 2 OCPs. Moreover, we found negative associations between fT4 levels and hexachlorobenzene concentrations. TBG concentrations were inversely related to 8 PCBs, 5 HO-PCBs, and 3 OCPs. Exposure to BDE-47 was positively related to tT3, whereas PFOS concentrations were negatively associated with TSH, tT3, and TBG and positively with fT4 concentrations. Conclusion: Exposure to several PHCs was associated with modifications of the thyroid parameters in adult Inuit, mainly by reducing tT3 and TBG circulating concentrations. The effects of PFOS and BDE-47 on thyroid homeostasis require further investigation because other human populations display similar or higher concentrations of these chemicals. [ABSTRACT FROM AUTHOR]