Recently, historians have focused on Warren S. McCul¬loch’s role in the cybernetics movement during the 1940s and 1950s, and his contributions to the develop¬ment of computer science and communication theory. What has received less attention is McCulloch’s early work in neurophysiology, and its relationship to his philosophical quest for an ‘experimental epistemology’ – a physiological theory of knowledge. McCulloch’s early laboratory work during the 1930s addressed the problem of cerebral localization: localizing aspects of behaviour in the cerebral cortex of the brain. Most of this research was done with the Dutch neurophysiolo¬gist J. G. Dusser de Barenne at Yale University. The con¬nection between McCulloch’s philosophical interests and his experimental work can be expressed as a search for a physiological a priori, an integrated mechanism of sensation.