Loosely based on true events in the eighteenth century, this novel chronicles the intersection of two lives. Charles O'Brien, an exceptionally large man, travels along with friends from Ireland to England to exhibit himself. He is a giant in more ways than one. In addition to his immense size, he is also intelligent, compassionate, articulate, and a gifted storyteller.

John Hunter, a Scottish anatomist and scientist, is obsessed with experimentation, discovery, and collection. He instructs graverobbers, dissects corpses, and self-experiments with syphilis. Although both men are remarkable and abnormal, it is the scientist rather than the giant who emerges as the genuine freak.

After the colossus dies, Hunter purchases O'Briens's body for study and his collection. At the end of the story, the giant's bones still hang in permanent display but Hunter's portrait is noted to be fading toward extinction.