The story begins in a futuristic domed city called Romdeau, built to protect its citizens after a global ecological disaster thousands of years ago. In this utopia, humans and AutoReivs (androids) coexist peacefully under a total management system. A series of murders committed by robots and AutoReivs infected with the Cogito virus (which causes them to become self-aware) begins to threaten the delicate balance of Romdeau's social order. Behind the scenes, the government has been conducting secret experiments on a mysterious humanoid life form called a "Proxy". The Proxy beings (described as God-like and Immortal) are believed to hold the key to the survival of mankind.
Re-l (pronounced "Rielle", also represented by the spelling "REAL" in the Romdeau citizen database) Mayer is assigned to investigate some of the murders with her AutoReiv partner, Iggy. She encounters a Cogito virus-infected AutoReiv and a fast and flexible monster. She later learns that the monster was a Proxy. The other central character, an immigrant named Vincent Law, is revealed to be connected in some ways with this Proxy. After being hunted down, Vincent lives for a while on the outside of the dome. He later leaves for Mosk, his birthplace, in an attempt to recover his memories. Re-l rejoins him to try to discover the truth behind the Proxies and the domes. It is revealed among other things that domes are all created by Proxies as well as the people inhabiting them who are created in special incubators.
In the Romdeau arcology, the government is divided between several entities: the Intelligence Bureau, the Health & Welfare Bureau, and the Security Bureau, are named in the series, all under the control of an Administrator who is referred to as the grandfather of "REAL".
The primary AutoReiv types are referred to as either 'Companion' or 'Entourage', depending on their role. There are others designed for leisure or combat functions; AutoReivs seem to be constructed of varying degrees of cybernetic complexity, as witnessed by AutoReivs on occasion producing blood splatter when shot and killed.
The humans in the city are grown in artificial wombs. Numerous times throughout the series it is stated that the humans living in the domes have no capacity to reproduce naturally. Likewise, when a new person is grown, they are done so to fulfil a specific purpose, thus ensuring that person's future place in society through a "raison d'être" (i.e., a "reason for being").