In 2012, the NIEHS established the multi-phased Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) Program to further address the role of the environment in disease susceptibility as a function of changes to the epigenome. The first phase of this program, TaRGET I (RFA-ES-12-008, TaRGET I: Chromatin Structure, Genomics, and Transcriptional Responses to the Environment), solicited and funded applications that support environmental health scientists' pursuit of research objectives aimed at understanding the environmental control of epigenetic mechanisms. These grants consider the impact of environmental toxicants on the following processes: nucleosome positioning, chromatin accessibility, chromatin remodeling and the role of non-coding RNAs. However, identifying exposure-induced changes in tissues/cells affected by disease is not always feasible in humans. The purpose of this Funding Opportunity Announcement is to establish the TaRGET II Consortium which will assess the utility of surrogate tissue epigenomic analysis as a means to examine the role of environmental exposures on epigenomic marks in target tissues. The goals are: to enhance our understanding of the relationship between exposure-induced perturbations of epigenetic marks in target versus surrogate tissues; determine conditions where these studies will be valid; and aid in the interpretation of the results of such studies. Applications submitted in response to this FOA must propose aims that focus on disease relevant environmental exposures and evaluate epigenomic changes or patterns of changes in surrogates that may serve as potential biomarkers of exposure associated pathologies. This FOA is published in parallel with a companion FOA, RFA ES-015-002, TaRGET II: Environmental Epigenomics Data Coordination Center (U24). Projects funded by these FOAs will collectively form the TaRGET II Consortium (T2C) and will develop a publically accessible database that provides data to the broader scientific community on the conservation of environmental exposure induced epigenomic changes in target tissues and cells and selected surrogates.