This chapter explores the historical emergence of the three R's, or the replacement, reduction and refinement of animal experimentation. It explores humane experimental technique through Foucault's notion of biopolitical governmentality, being the government of the self by oneself in its articulation with relations with others. The three R's, when first articulated in the 1950s as humane experimental technique, provided a systematic framework which sought to establish ethical concerns as a constitutive part of the epistemology of animal-dependent science. The chapter focuses the experimental encounter, that can be understood not only as the medium in which the nonhuman animal was constituted and cared for but equally, and interdependently, as the site where the knowing human subject was similarly constituted and cared for. Humane experimental technique was the second phase of a project to develop a science of animal welfare by the London-based Universities Federation for Animal Welfare (UFAW).