How does Locke contribute to the development of projects for a science of the mind, even though he seems to reject or at least bracket off such an idea himself? A canonical empiricist, Locke nevertheless goes out of his way to state that their project to investigate and articulate the ‘logic of ideas’ is not a scientific project: “I shall not at present meddle with the Physical consideration of the Mind” (Essay, I.i.2). Locke further specifies that this means his analysis of mental processes will not engage with knowledge of the brain, even though he had been the student of Thomas Willis. Now, Kant seemed to make an elementary mistake, given such a clear statement on Locke’s part, when he claimed that Locke’s project was a “physiology of the understanding” (in the Preface to the A edition of the first Critique). One can ask of course what this physiology of the understanding was, and if it existed, in or out of the Lockean intellectual world. This leads me to inquire, not into the well-studied fortunes of Locke’s idea of thinking matter, but into the outcome of his empiricism for a scientific treatment of the mind, including in the sense of a process of ‘naturalization’ of the mind (with implications also for our understanding of empiricism). Because if Kant made this charge, there were also many 18th-century thinkers who positively treated Locke as their great forerunner in psychology and related fields: Charles Bonnet and Joseph Priestley among them, just as some prominent physicians such as Cabanis claimed to be ‘finishing the job’ that Locke had started in, e.g. their materialist theories of the passions. What one might term ‘the Locke Problem’ here is: how can one reconcile empiricism and claims about cerebral processes, while seeking to remain a Lockean?