In this article we describe a research partnership between the Akwesasne Mohawk Nation and scientists at the University at Albany, State University of New York, initiated to address community and scientific concerns regarding environmental contamination and its health consequences (thyroid hormone function, social adjustment, and school functioning). The investigation focuses on cultural inputs into health disparities. It employs a risk-focusing model of biocultural interaction: behaviors expressing cultural identity and values allocate or focus risk, in this instance the risk of toxicant exposure, which alters health status through the effects of toxicants. As culturally based behaviors and activities fulfill a key role in the model, accurate assessment of subtle cultural and behavioral variables is required and best accomplished through integration of local expert knowledge from the community. As a partnership project, the investigation recognizes the cultural and socioeconomic impacts of research in small communities beyond the production of scientific knowledge. The components of sustainable partnerships are discussed, including strategies that helped promote equity between the partners such as hiring community members as key personnel, integrating local expertise into research design, and developing a local Community Outreach and Education Program. Although challenges arose during the design and implementation of the research project, a collaborative approach has benefited the community and facilitated research.