A wide array of federal mandates have a profound impact on the use of racial and ethnic categories in biomedical research, clinical practice, product development, and health policy. Current discussions over the appropriate use of racial and ethnic categories in biomedical contexts have largely focused on the practices of individual researchers. By contrast, our discussion focuses on relations between the daily practices of biomedical professionals and federal regulatory mandates. It draws upon the legal doctrine of equal protection to move beyond such debates and to propose guidelines to address the structural forces imposed by federal regulations that mandate how data about race and ethnicity are used in biomedical research. It offers a framework to manage the tension involved in using existing federally mandated categories of race and ethnicity alongside new scientific findings about human genetic variation.