Infectious Affect: The Phobic Imagination in American Literature begins with this question: by what literary pathways did the -phobia suffix come to shape U.S. politics so profoundly? In current political discourse, Americans rely on phobia as a concept to describe conditions of social inequality. People and policies that negatively impact communities based on sexual orientation, gender identification, ethnicity, race, or religion are understood to be homophobic, transphobic, xenophobic, or Islamophobic. However implicitly, these terms also aspire to a widely accepted hypothesis: in short, that systemic inequality begins with and is sustained by a nucleus of fear, on the part of those wielding the greatest political power. Taking part in the new philological turn in literary studies, my dissertation shows that the –phobia suffix first began to be adapted from medical literature to explain sociopolitical phenomena in the late 1700s, then went on to catch on rapidly in the antebellum period. At the same time, in tracing this history we discover that phobia’s proliferation as a political category did not go uncontested. I take less interest, then, in those who played by the rules of a consolidating phobic imagination than I do in writers who repurposed it to counterintuitive ends. In telling the backstory of activist phobias, Infectious Affect explores the rise of a phobic imagination in medical, literary, and political contexts alike, proposing that phobia activated a new dynamism between disparate modes of knowledge production.