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The National Institute of Environmental Health Sciences (NIEHS) is the leading biomedical research institution in the United States whose mission is to support research that seeks to understand how environmental exposures affect human health. NIEHS possesses a longstanding interest in the health effects of agrochemical and other environmental exposures in rural America, including pesticides, to farmers and their families and to migrant farmworkers and their families. In recent years, NIEHS has begun augmenting traditional basic science investigations with innovative programs that translate findings from the laboratory to affected populations. It is through community-based participatory research that NIEHS strives to advance the public health field by fostering the development of culturally relevant interventions that will reduce exposures to environmental contaminants and the risk of environmentally induced disease. In this article, we describe the translational research program at NIEHS as it relates to the NIEHS mission and highlight activities pertinent to the health of rural communities, especially underserved populations. We provide an overview of NIEHS-supported projects addressing health concerns of Native American and rural African-American communities in addition to farmworkers. We conclude with a discussion of future plans for community-based participatory research at NIEHS.