Background: An increasing number of studies are reporting the existence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (HO) and methoxylated (MeO) metabolites in the environment and in tissues from wildlife and humans. Objective: Our aim was to characterize and compare the agonistic and antagonistic activities of principle PBDE congeners and their HO and MeO metabolites against human nuclear hormone receptors. Methods: We tested the hormone receptor activities of estrogen receptor a (ERα), ERβ, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor α₁ (TRα₁), and TRβ₁ against PBDE congeners BDEs 15, 28, 47, 85, 99, 100, 153, and 209, four para-HO-PBDEs, and four para-MeO-PBDEs by highly sensitive reporter gene assays using Chinese hamster ovary cells. Results: Of the 16 compounds tested, 6 and 2 showed agonistic activities in the ERα and ERβ assays, respectively, and 6 and 6 showed antagonistic activities in these assays. 4'-HO-BDE-17 showed the most potent estrogenic activity via ERα/β, and 4'-HO-BDE-49 showed the most potent antiestrogenic activity via ERα/β. In the AR assay, 13 compounds showed antagonistic activity, with 4'-HO-BDE-17 in particular inhibiting AR-mediated transcriptional activity at low concentrations in the order of 10⁻ɸ M. In the GR assay, seven compounds, including two HO-PBDEs and two MeO-PBDEs, showed weak antagonistic activity. In the TRα₁ and TRβ₁ assays, only 4-HO-BDE-90 showed weak antagonistic activity. Conclusions: Taken together, these results suggest that PBDEs and their metabolites might have multiple endocrine-disrupting effects via nuclear hormone receptors, and para-HO-PBDEs, in particular, possess more potent receptor activities compared with those of the parent PBDEs and corresponding para-MeO-VBDEs.