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To what extent has medical knowledge structured colonial relations? This article explores the social construction of infectious diseases not only as biological phenomena, abstracted from the social world but co-produced by it. In doing so it expands sociological theories of health and medicine, incorporating theories on race and empire into critiques of scientific and medical knowledge production. Examining treatises produced on early tropical medicine and the emergence of the field of study itself demonstrates how the production of knowledge on this topic operated as a project of empire and more significantly, to redefine the space and peoples of the colonized world relative to the colonizer for the purpose of sanitary control, labor exploitation and in order to protect colonial forces from the diseases they saw as endemic to the tropical world. Treatises on tropical diseases designed for the protection of European populations envisioned a foreign space that needed to be rendered safe for habitation but was at its core threatening to a European population–a space apart and alien. Conversely treatises on slave health management and writings upon the health of the colonized explored the natural proclivities of those of the tropics to endure and survive colonial labor and enslavement. Disease, susceptibility to it and the nature of its effects became a way of understanding the differences between European and colonial populations from Columbus’ arrival until the latter nineteenth century. In the tropics, European’s saw in themselves a weakness for diseases emerging from their climes and thus required a mode of rule, located not only in economic and military conquest but also in sanitary order. This dictated relations not only to colonial space but also to the enslaved and colonized that maintained the colonial project, defining roles and systems of governance.