The Fall of the House of Usher follows an unnamed narrator to the house of Roderick Usher, a friend who suffers from some strange malady. It is a family sickness, and its symptoms include acute anxiety, hypochondria, and extreme sensitivity to light and sound. Roderick's twin sister, Madeline, is also ill, and suffers from death-like trances. Soon we are propelled through a horrifying tale of a house which has taken on the sins and sickness of its inhabitants.

Much analysis of this story has been done, as it explicitly concerns the human psyche - so the house is the unconscious, or the soul, and the eventual destruction which occurs is caused by mental disorder stemming from possible vampirism or even incest. Regardless of the analysis, Poe's vivid and macabre tale is a central masterpiece of American Gothic literature, and is considered his most famous work of prose.