PROJECT SUMMARY/ABSTRACT Individual institutions across the country have worked to support research in a wide variety of areas, including precision medicine research, by developing large biorepositories comprised of biospecimens and health data collected from local patients and controls. However, these local cohorts rarely provide the diversity and size needed to identify and study subsets of patients who share biological mechanisms for their disease, and are thus more likely to respond to the same targeted therapies. To address this need, researchers have begun to promote the networking of multiple repositories within or across multiple institutions. This networked biorepository approach makes it possible for researchers to access larger, more diverse sets of data and biospecimens in a way that leverages the research relationships that local institutions have built with their own communities of donors. In order for this approach to be successful, networked biorepositories need to address important ethical, legal, and social challenges. Networked biorepositories are comprised of diverse sets of specimens and data from different institutions, each with their own governance structures and donor needs. For these reasons, they encounter complex issues related to consent and donor permission, privacy and data security, and data access. These novel challenges have not previously been examined in detail, and best practices for addressing these issues through governance and oversight processes are lacking. This study will address these important needs through a rigorous, mixed-methods study of the perspectives and experiences of stakeholders currently engaged in designing, operating, and governing networked biorepositories. It will also aim to develop approaches to consent and donor permission, privacy and data security, data access, governance, and oversight that are most appropriate and effective for a variety of networked biorepository configurations.