Culture and human behavior are recognized today as major forces acting on human biological variation around the world. Studies of the relationships between biology and processes, such as modernization, urbanization, and social stratification, are prominent in our journals and meetings. An ongoing study of the interrelationships between toxicant exposure (organochlorines, lead, and mercury), health, and culture among youth of the Mohawk Nation at Akwesasne is located within this context and is used to analyze the strengths and challenges of a partnership approach to biocultural research. To assist in modeling the complex relationships between health, behavior, and culture, we have employed concepts from contemporary social theory, integrated qualitative and quantitative research, and implemented community-based research principles to develop a partnership approach to research in human biology. The community is directly involved in identifying research goals, developing research protocols appropriate for local cultural sensitivities and complexities, implementing the protocols in the field, and collaborating in the analysis and publication of results. We show the utility of this approach for understanding the relationships of toxicants to behavior and biological outcomes (adolescent growth, sexual maturation, and endocrine system alteration); as well as how it facilitates the agency of participants and communities involved in research, and brings greater social engagement to the development of the new human biology. Am. J. Hum. Biol. 19:511–524, 2007. © 2007 Wiley-Liss, Inc.