This American literature dissertation offers an account of the critical category of "experimental literature," arguing that, nebulous as the term appears to be, it is rooted in ideas of scientific experiment that were under debate in the late nineteenth and early twentieth centuries. While experimental literature is often described in terms of "formal innovation," this dissertation reads literary form not as an autonomous category in its own right but as an indicator of epistemological investments. Borrowing Lorraine Daston and Peter Galison's concept of the "epistemic virtue," this dissertation argues that experimental literature seeks to produce a "sense of the real," not by thematically treating scientific ideas or even by emulating scientific methods, but rather by using literary form to negotiate the changing landscape of what constituted scientificity in the first place. Epistemic virtues are the investments, at once methodological and ethical, that define the experimental mode. Experimental authors, this dissertation argues, seek ways for literature to produce knowledge with strong epistemic guarantees. The dissertation begins by reading Émile Zola's Nana as an early articulation of how literature might engage in research. Nana reveals the centrality of the epistemic virtue of objectivity to Zola's project, as well as a surprising symbiosis between objectivity and spectacle. A chapter on Gertrude Stein's undergraduate and graduate scientific research and early writings (through Three Lives) shows that a naturalist version of experimentalism feeds directly into Stein's modernism. A chapter on the poetry of Marianne Moore argues that precision is the key epistemic virtue that Moore deploys, and that precision's refusal of hierarchy and negotiation of "high" and "low" cultural forms has underwritten the ambivalent reception history of her work. The final chapter reads William Carlos Williams's late poem Paterson together with Boasian anthropology to argue that Williams's late poetic image operates as a means of guaranteeing presence.