Exposure to chemicals that affect the endocrine system (e.g., environmental estrogens) is postulated to have broad impacts on human health. One such compound is Bisphenol A (BPA), which is an important industrial compound at the epicenter of a heated debate over the potential for environmental endocrine disruption. In industrialized nations, more than 90 percent of the population is exposed to BPA, fueling concerns that internal exposure to bioactive BPA may be high enough to cause toxicity. With BPA as a case study, this symposium explores whether emerging research from the affiliated disciplines of exposure science, epidemiology, toxicology, and computational biology can together resolve the debate over environmental endocrine disruption. This session will introduce the BPA cause célèbre, present new epidemiological data, and present new rodent toxicity studies that directly relate toxicity with internal exposures to BPA and ethinylestradiol, a potent reference estrogen. These findings are contrasted with emerging data on internal exposures to the bioactive form of BPA in humans and the metabolism and pharmacokinetics of BPA in adult, neonatal, and fetal rodents and nonhuman primates. These data will be synthesized and used critically to examine the hypothesis that human internal exposure to bioactive BPA is sufficiently high to produce a demonstrably adverse health outcome. Finally, the broader application of this cross-disciplinary framework to other potential endocrine disruptors will be discussed.