While working on a collaborative AIDS research project in Malawi in 2005, I was struck by the noticeable differences in how the risk of contracting AIDS was interpreted by members of the research team, despite their sharing of the same research agenda, protocols, and directives. What this suggested to me was not simply that scientific inquiry is inherently social but rather how collaboration is inevitably paradoxical. Collaborative research entails a central contradiction between the need for a unified agenda and the panoply of cultural viewpoints that aspire to be incorporated. This contradiction points to a question central to this particular project and to the conduct of collaborative research more generally: In the face of contrasting and possibly discordant presuppositions concerning the central focus of research, how does one (or more) of them gain legitimacy? Critiques of top-down AIDS research in sub-Saharan Africa gave rise to collaborative research in the 1990s. Donors and national governments increasingly insist that research be collaborative and culturally relevant, yet they lack detailed knowledge of how different understandings of culture, and especially in the case of AIDS, different understandings of risk, are negotiated in the context of research practice. While collaborative research may begin with varying interpretations across collaborators, during the research process certain interpretive explanations are taken as authoritative. My research considers how different constructions of risk are produced and communicated among various levels of international AIDS research in Malawi. How are diverse theories and perspectives of risk produced, challenged or confirmed as authoritative knowledge in the interactions among actors located within four levels of the research infrastructure in Malawi?