This essay examines the degeneration thesis, as formulated by Buffon and taken up in the so-called dispute of the New World. Early colonial observers such as Acosta and Catesby engaged with the classical climate-determinist paradigm, with its north–south orientation of climate zones. Buffon drew on these natural history observations, Enlightenment social theory, and the new geoscience and reoriented climate determinism on an east–west axis. Buffon posited that America had emerged more recently than Europe from oceanic submergence and was thus colder and wetter – and that therefore America’s climate was more favorable to the production of supposedly inferior animals such as insects and reptiles and less favorable to larger mammals and humans. Implications for human development were vigorously contested by Americans such as Jefferson and reoriented again along a global north–south axis, notably by Hegel. The degeneration thesis enjoyed a long legacy, surfacing in the United States in nativist-populist responses to demographic issues. The essay concludes by identifying two such episodes, early twentieth-century nativism and the new nativism of the twenty-first century.