P-259 Introduction: Subsistence lifestyles often rely on the use of ecosystem resources to obtain the necessities for individual or community wellness. There is increasing awareness that lifestyles and cultural practices associated with subsistence may lead to significantly increased health risks. This may be due to multiple cross-media exposures occurring when members of subsistence-based communities conduct culturally relevant activities. This is particularly apparent when considering the fish consumption and dietary intake of Tribal communities, as there are a variety of fish baiting, catching, cleaning, storing and preparing techniques. To elucidate the ways in which subsistence populations are differentially exposed to toxics, the U.S. Environmental Protection Agency and Centers for Disease Control and Prevention launched a novel research initiative to develop more refined exposure methodologies while concomitantly exploring risk mitigation options that are appropriate to subsistence populations. Methods: This research portfolio was designed to encompass traditional and non-traditional scientific approaches to collect baseline data that link culture and exposure. For example, collection and chemical analysis of multiple whale, walrus, seal, and reindeer tissues, including muscle, blubber and organ samples, are being conducted in Northern and Western Alaska in partnership with Saint Lawrence Island Yupiks and Inupiat hunters. A scientifically based, eco-cultural zone map across the United States is in the final stages of development for the purposes of more refined exposure and quantitative risk assessment. Developing ecoregion-specific subsistence exposure scenarios integrates a combination of baseline ecological descriptions with anthropologically defined information on subsistence lifestyle and diet. A mercury risk intervention study in the Great Lakes region is using GIS mapping to inform Tribal decisions for subsistence fishing. Results: These local and national-level projects represent EPA's first efforts in systematically incorporating cultural practices of sequestration, consumption, and use of foodstuffs in conducting research. The researchers have quantified contaminant sources, identified unique exposure pathways, and conducted dietary and cultural surveys. They are currently translating the analytical chemistry data on foodstuffs and environmental media for tribally-based risk assessments and will link sources to pre-existing biological data. The results will lead to the development of risk management strategies that identify the healthiest ways to practice and maintain the cultural and traditional lifestyles of Tribal communities. Discussion: Subsistence populations live disproportionately near Superfund or other toxic sites. The lifestyles and cultural practices of Tribal populations are qualitatively distinct and can consequently, modify their risk. However baseline information on exposure sources, pathways and variation is needed before causal relationships between individual/cumulative toxic exposures and wellness outcomes can be tested. These studies are an important step toward building Tribal capacity to conduct large-scale community-driven exposure, epidemiology and intervention studies that consider the economic and cultural needs and traditions of their communities.