- Background: Reliance on natural resources brings Native American communities into frequent contact with environmental media, which, if contaminated, represents an exposure route for environmental pollutants. Native American communities vary in their perspectives on research and relatively little is known about the range of perspectives regarding the use of biological samples for environmental exposure assessment. Methods: Thirty-one members of Zuni Pueblo (median age = 40.0 years, range = 26⁻59 years) participated a series of four focus groups. Qualitative themes emerging from the focus group discussion transcripts were identified by content analysis. Results: Emergent themes included adequate informed consent, traditional beliefs, and personal choice. Conclusions: The discussions reinforced the central role of traditional values in the decision to participate in research involving biological samples for environmental exposure assessment. Decision-making required a balance between the perceived value of the proposed project and its purpose, with cultural perspectives surrounding the biological sample requested. We examine the potential for study bias and include recommendations to aid in the collaborative identification and control of unintended risks posed by the use of biological samples in environmental health studies in native communities.