Salmacis is introduced early on. It monitors the H.M.S. Exodus to attempt to study the Indisen onboard. It also meets Jordan there and informs him that the majority of Fears want to kill him for defeating the Harlequin earlier, assuring him that it herself doesn't mind him because it has no emotional attachment.
Salmacis then assists the protagonists in locating the Seven Ciphers and warns them of plans from more malevolent Fears in Sanctuary Francisco.
During the period of the Knights of Xanadu, Salmacis begins to manipulate the protagonists for her own benefit. It selectively speaks to Jordan with Camper it thinks he'll react well to, eventually creating the iconic blue-haired Camper shown in art. At the same time, her own emotions become more pronounced.
It focuses a while on discovering the identity of Indisen, hiding key information about Rapture from the protagonists, and terrorizing other humans. When Fentzy gets upset at Jordan, Salmacis comforts him and proceeds to sleep with him. In Finland after the Neonate deliver the Pacific into the Topography Genera Center North, it protects Jordan and reveals her affection for him. In an act of desperation upon realizing the gravity of her mortality in the Topography Genera Center South, it goes as far as to ask him out.
During Tiresias's periodic narration, Salmacis is shown years later to be a substantial Fear in managing the Earth, though in her private life it seems to be drugging Jordan with her ink, possibly coaxing him to become a Camper.