Bisphenol AF is a homologue of bisphenol A and is used in the production of trifluoromethyl-containing polymers. Although much is known about the toxicity of bisphenol A, little toxicological information is available on bisphenol AF. Matsushima et al. (p. 1267) determined the relative preference of bisphenol AF for the human nuclear estrogenic receptors ER? and ER? and the bisphenol A–specific estrogen-related receptor ERR?. The authors found that bisphenol AF strongly and selectively binds to ERs over ERR?. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ER? than for ER?. When examined using a reporter gene assay, bisphenol AF was a full agonist for ER?. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ER?. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ER? agonist 17?-estradiol. Results suggest that bisphenol AF could function as an endocrine-disrupting chemical by acting as an agonist or antagonist to perturb physiological processes mediated through ER? and/or ER?.