Background The idea of grafting animal tissues onto humans has a long history of mythological legends but also empirical surgical experiments. This article aims to renew existing historiography on this subject (Gibson, 1955; Deschamps et al., 2005; Cooper et al., 2015) by specifically addressing xenograft research carried out in France during the 1870s. Methodology A qualitative study of a corpus of historical sources was conducted. This corpus consisted of a set of doctoral medical theses defended in the latter half of the 19th century as well as a selection of articles from 19th century specialized medical press. Results The second half of the 19th century was a time of radical transformation in the understanding of grafts in French medical circles, informed by advances in clinical surgery and experimental physiology. In the wake of these profound epistemological upheavals, several xenografts were attempted on humans in 1870s France, using a wide variety of animals such as rabbits or dogs in order to treat conditions with a high chance of relapse. This article seeks to explain why these xenografts emerged at that precise moment in French medical history, while also analyzing the factors and assumptions underlying their rise. Conclusion The notion of adhesion combined with the absence of the concept of rejection explain the implementation of these trials and their continuation in Europe and the United States well after the 1870s. This article brings a historical perspective to contemporary xenotransplantation attempts.