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Denis Diderot’s 1749 essay La Lettre sur les aveugles à l’usage de ceux qui voient (Letter on the Blind for the Use of Those Who Can See) examines three blind figures, in the process laying the foundation for his materialist hermeneutic. Although many academic works of recent decades have focused on skepticism and materialism in Diderot’s oeuvre broadly–and in the Lettre specifically–to date, few have reckoned with the materiality of machines and their role in the production of this new form of knowledge. The Lettre examines not only the ways in which language expresses itself through the human body but also the ways in which the body engages with tools and machines in order to liberate expression and knowledge from the body itself. These machines exist in prosthetic relation to the body, and this intracorporeal relation posits a view of disability that is enabling. In this essay, I examine Lettre sur les aveugles, arguing that in form and in content, Diderot proposes a prosthetic ethos that breaks down distinctions between organic and inorganic matter. Placing Diderot into dialogue with Bernard Stiegler, particularly regarding the latter's work on mnemotechnics, I demonstrate how in Diderot’s Lettre, materialist knowledge emanates from a delicate and intense relation between disabled bodies and machines.