The aim of this article is to investigate in some detail the origins of Frank H. Knight's antipositivism and to assess the main influences that brought him to a change in methodological perspective after 1921. As importantly, the article also attempts to increase our general understanding of the methodological debates taking place during the early decades of the last century and to shed new light on the inherently pluralistic character of US interwar economics. The first section outlines Knight's methodological views as presented in his early works; the second section discusses Knight's “recantation” and his attack on behavioristic social science; the third section analyzes Knight's discussion of the nature and limitations of scientific economics; the fourth section offers a brief digression on Knight's relationship with American institutionalism; the fifth section deals with the later developments of Knight's antipositivism; the final section presents some conclusions.