In this article, I develop a feminist posthumanist account of biomedical policymaking as a material-discursive intervention that shapes the emergence of phenomena in the scientific laboratory. The setting is United States (U.S.) biomedicine, where a recent policy of the National Institutes of Health has mandated the consideration of sex in basic and preclinical research. Called Sex as a Biological Variable (SABV), the mandate configures cell lines and animal models as the next frontier in the project of advancing gender equity in biomedical research. Given sex and gender are increasingly recognised as having complex, entangled, and dynamic effects on human health and illness, how do laboratory animals respond to their attempted enrolment in this regulatory intervention? Through a qualitative analysis of this policy domain, I show how laboratory animals reveal the context-specific character of sex, its multiplicity and elusiveness as a so-called biological variable, and the considerable work needed to shore up human ideologies of sex as a pervasive cross-species form of binary difference. I suggest that while regulatory interventions constrain patterns of mattering, they also serve as agential openings in which laboratory animals can 'kick back' and reconfigure the pursuit of knowledge, particularly as it relates to difference and health.