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This thesis is a social history of disease and mortality in the American Deep South before the Civil War. Yellow fever attacked the region at epidemic levels every two or three years between 1800 and 1860, killing about eight percent of the urban population, and as many as 20 or 30 percent of recent migrants from Europe. With little epidemiological understanding of mosquito-borne viruses—and almost no public health infrastructure to ameliorate disease—the only real protection from this scourge was to "get acclimated": fall sick with, and survive, yellow fever. About half of all people would die in the acclimating process. By placing the Deep South within an Atlantic disease diaspora uncontained by continental boundaries, the project shifts the fault-lines of the Southern past from North-South political conflicts onto similarly formative but overlooked ecological processes in the Greater Caribbean. Yellow fever and mass mortality are largely absent from the recent historiography on the cotton kingdom and "slave racial capitalism." But as well as being a “slave society,” this thesis suggests the Deep South was also a "disease society": Deep Southerners discussed yellow fever obsessively, worked according to its seasonal schedule, and judged others based on their perceived vulnerability to the disease. Yellow fever, and immunity to it, profoundly shaped the asymmetrical hierarchies of Deep Southern society, with acclimated "immunocapitalist" creoles on top, and unacclimated "foreigners" below. Slavers and their allies argued only intellectually-inferior but naturally-resistant black people could perform the arduous labour of sugar and cotton cultivation in the Deep South, as whites too frequently died. This became the region's chief argument for permanent racial slavery. However, almost every slave revolt in Louisiana coincided with a particularly bad epidemic, suggesting slaves found disease politically intriguing and understood that yellow fever left white society chaotic and vulnerable to attack.