ABSTRACT. May scientists rely on substantive, a priori presuppositions? Quinean naturalists say "no," but Michael Friedman and others claim that such a view cannot be squared with the actual history of science. To make his case, Friedman offers Newton's universal law of gravitation and Einstein's theory of relativity as examples of admired theories that both employ presuppositions (usually of a mathematical nature), presuppositions that do not face empirical evidence directly. In fact, Friedman claims that the use of such presuppositions is a hallmark of "science as we know it." But what should we say about the special sciences, which typically do not rely on the abstruse formalisms one finds in the exact sciences? I identify a type of a priori presupposition that plays an especially striking role in the development of empirical psychology. These are ontological presuppositions about the type of object a given science purports to study. I show how such presuppositions can be both a priori and rational by investigating their role in an early flap over psychology's contested status as a natural science. The flap focused on one of the field's earliest textbooks, William James's Principles of Psychology. The work was attacked precisely for its reliance on a priori presuppositions about what James had called the "mental state," psychology's (alleged) proper object. I argue that the specific presuppositions James packed into his definition of the "mental state" were not directly responsible to empirical evidence, and so in that sense were a priori; but the presuppositions were rational in that they were crafted to help overcome philosophical objections (championed by neo-Hegelians) to the very idea that there can be a genuine science of mind. Thus, my case study gives an example of substantive, a priori presuppositions being put to use—to rational use—in the special sciences. In addition to evaluating James's use of presuppositions, my paper also offers historical reflections on two different strands of pragmatist philosophy of science. One strand, tracing back through Quine to C. S. Peirce, is more naturalistic, eschewing the use of a priori elements in science. The other strand, tracing back through Kuhn and C. I. Lewis to James, is more friendly to such presuppositions, and to that extent bears affinity with the positivist tradition Friedman occupies.