Their appearance is similar to humans, but with several differences, namely horn-like protrusions on the forehead and the presence of telekinetic invisible arms called "Vectors". One such Diclonius, Lucy, is the main character of the series: Initially held in a facility built for experimentation, located off the coast of Kamakura, she manages to escape and wreak havoc, but is injured in the process, an event which causes her to develop a secondary, childlike personality known as Nyu.

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Lucy is found by two locals, Kouta, who studies at the local university, and his cousin Yuka. They take her in, and become involved with the numerous, often brutal, attempts to recapture her by a Special Assault Team and a number of other Diclonius, who shift frequently from oblivious to murderous.