Our objective is to provide a centralized, publicly available resource with comprehensive, well-annotated data and analysis tools that informs design and interpretation of environmental health studies and promotes novel insights into the etiologies of environmentally influenced diseases. Most human diseases involve interactions between genetic and environmental factors; however, the basis of these complex interactions are not well understood and limit improvements in toxicity prediction, risk assessment, research prioritization and therapeutic interventions. We developed the Comparative Toxicogenomics Database (CTD; http://ctdbase.org) to enhance understanding about environment-disease connections by providing manually curated data describing chemical-gene interactions and chemical- and gene-disease relationships from the peer-reviewed literature and integrating these data with select external data sets (e.g., pathways and biological process data) and novel data analysis tools. We propose to develop and implement a new module of manually curated data describing cross-species chemical-phenotype information and analytical capabilities that will incorporate these data into the broader biological context of CTD. These additions will significantly increase the impact of CTD and specifically aim to advance: a) understanding of environmental disease progression via pre-disease phenotypes, b) identification of potential biomarkers of exposure, c) the capacity to conduct and interpret studies across species and experimental systems, and d) development of biological networks that associate chemicals, genes, phenotypes, and diseases. This project will leverage our interdisciplinary team's expertise in toxicology, software development, curation, bioinformatics and statistics, as well as the flexible infrastructure and demonstrated value of CTD to facilitate understanding of critical environmental health issues in direct alignment with emerging research priorities.