The paper offers a reading of Thomas Pynchon’s Mason & Dixon (1997) in terms of its portrayal of technology, science, and, more broadly, Enlightenment thought. The argument is that the novel’s main concern is the inability to separate science out from the culture in which it is practiced and that scientific and technological progress are therefore deeply vulnerable to exploitation by political and economic systems. This conjunction of science, culture and politics is evinced by considering three principal matters. Firstly, Mason’s and Dixon’s surveying of the notorious border between Pennsylvania and Maryland is explored, as is the way their work figures in American eighteenth-century history and culture, in relation to the revolutionary activity, land ownership, slavery, westward movement, relations with Native Americans, etc. Secondly, the paper assesses the way Pynchon’s two astronomers are implicated in a grander process of eighteenth-century globalization and the creation of the nascent British Empire. Finally, more abstract and indeed more pervading effects of the Age of Reason on eighteenth-century culture presented in the novel are considered, together with various ways of countering the totalizing effects of ‘Enlightened’ thought. Pynchon, it is shown, is in his novel exploring the differences between what the development of science in the period should have represented in its ideal version, and what it really represented—the establishment of power relations.