Malaria transmitted by mosquitoes was one of the most significant health threats to soldiers on both sides of the American Civil War, with an estimated 1.3 million Union cases of malaria recorded during the conflict. The disease was particularly devastating in the swampy lowlands of Virginia, the Carolinas, and the Deep South, where Anopheles mosquitoes were abundant. Union forces stockpiled enormous quantities of quinine to control the disease, and the logistical management of malaria was a significant factor in military planning and campaign outcomes.

Walt Whitman's experience as a nurse in the Civil War hospitals exposed him to the full range of diseases afflicting soldiers, including malaria, and his poems in Drum-Taps and his prose in Specimen Days reflect the atmosphere of epidemic disease in wartime. Ambrose Bierce, who served in the Union Army and contracted malaria, brought a sharp awareness of biological suffering alongside military horror to his short stories about the war. The mosquito's role in the Civil War became part of the broader tradition of American writing that saw nature as both the setting and the agent of historical drama.