An approach to using mode-of-action (MOA) information across animal species has been developed to support both integrated ecological and human health assessment methods development and cross-species extrapolation for human health assessments. By assessing the effects and MOA data for a given toxic agent, the relationship between MOA and species relatedness (i.e., evolutionary relationships) can be determined. A case study assessing the utility of this approach was performed for bisphenol A (BPA). BPA, a component of polycarbonate plastics, epoxy resins, and polyester resins, was selected because it is a high production volume chemical; data have been identified for both vertebrate and invertebrate species; and the estrogen agonist MOA (i.e., binding and activating the estrogen receptor to transcribe estrogen-responsive genes) has been well described for a number of vertebrate species. Cross-species MOA information for developmental and reproductive effects of BPA, limited to the animal kingdom, was reviewed from the literature, and the relationship between species relatedness and MOA was assessed. assessed. MOA was defined as the key step in the toxic response after chemical interaction at the target site that is responsible for the physiological outcome or pathology. Reproductive and/or developmental in vivo effects data for BPA were identified for 16 species representing seven animal classes (gastropods, crustaceans, insects, amphibians, fish, birds, and mammals) in three phyla (mollusks, arthopods, and chordates). This report was developed in support of EPAs Office of Research and Developments Multi-Year Plan for Endocrine Disruptors (2003).