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In light of the second Trump administration’s attempted purge of DEI efforts from the federal government, our paper revisits the “inclusion-and-difference paradigm” (Epstein 2007) of biomedical science by examining recent organizational struggles at the NIH. Beginning in the 1980s, federal science and health agencies institutionalized policies requiring the inclusion of women, racial and ethnic minorities, children, and the elderly in biomedical research and discouraging the extrapolation of research findings from one group to others. These reforms reshaped grant making, research practices, drug approval processes, and bureaucratic infrastructures, embedding logics of group-based difference and egalitarian representation within the organizational epistemics of federal biomedical science. We ask how organizational actors at the NIH are interpreting, contesting, and potentially reworking the inclusion-and-difference paradigm under conditions of explicit political hostility to DEI. To what extent have the policies, offices, and procedures that institutionalized inclusion been upended, reframed, or maintained? Taking the NIH as an epistemic, racialized, and gendered organization, we examine how shifting political currents shape what kinds of group difference are studied or not and under what terms. Drawing on analysis of government reports, biomedical journals, ethnographic observation at science policy events, and semi-structured interviews with current and former NIH employees, we argue that the inclusion-and-difference paradigm has been unevenly destabilized, with examination of racial health equity especially targeted, questions of sex and gender reformulated in an anti-trans direction, and age-based inclusion comparatively insulated. In addition, organizational struggles push and pull in different directions: public-facing pronouncements of political appointees diverge significantly from the beliefs and practices of rank-and-file employees, who can partially resist the undermining of the inclusion-and-difference paradigm. Our study underscores how organizations mediate between political developments and changes in scientific practice and, in turn, how they govern the production of knowledge and ignorance about human health and human difference.