<p>This study explores animal research professionals’ attitudes toward the 3R principles (i.e., 3R: replacement, reduction, and refinement of the use of animals in research) using an experimental ethics approach. A thought experiment involving a superior extraterrestrial alien species conducting research on humans according to 3R was presented to 13 Swiss-based animal research professionals (i.e., researchers using animals, veterinarians, animal welfare officers, 3R coordinators, animal science trainers, and members of animal experimentation commissions) during qualitative semi-structured interviews. Participants were asked to reflect on whether the aliens’ research is justified, as well as on the extent to which 3R is the right framework for it. Thematic analysis was used to analyze the data. Participants revealed a spectrum of attitudes, ranging from ambivalent acceptance to outright rejection of “3R for humans”. Key themes included concerns about legitimacy, consent, and power asymmetry, as well as anthropocentric and speciesist attitudes. These findings support previously identified concerns about the limitations of 3R and show that professionals also recognize these challenges when reflecting on the issue using a role-reversal thought experiment. This underscores the ongoing need to advance ethical frameworks in animal research, expanding beyond 3R to incorporate broader moral considerations. Ultimately, our findings suggest that empirical animal ethics, and in particular thought experiments of this kind, offers a promising route to fostering ethical reflection and reform.</p>