Saito was in charge of research involving Mariko and often communicated with her through the use of loudspeakers. Mariko always referred to Saito as "Mommy" during these interactions. She also took steps to undo any parental feelings Mariko may have retained towards her birth parents, Kurama and Hiromi, telling her they abandoned her in an attempt to endear herself to the toddler.
When told by Shirakawa that the project had decided to use Mariko as a means of retrieving Lucy, Saito was the first to greet her upon her emergence from total isolation despite lingering doubts that anyone could control her. Seemingly overjoyed at seeing her "mommy" for the first time, Mariko's true thoughts would soon be known. Saito continued to assume she had the sort of control a mother would have over her and encouraged her as she tried to use her emaciated body to hobble over. Once Saito approached closely enough, Mariko revealed her true intentions. The girl asked if Saito were her mother, and Saito responded she was, only to be told by a giggling Mariko that she was not. Mariko then split her body above the waist and threw her upper torso through the glass window within the operations and control room to startle the guards. To prevent Mariko from escaping and causing any further damage, the dying Saito detonated the explosive in Mariko's right arm to subdue her. In the manga, during the operation to recapture Lucy, Isobe, Kurama's assistant, overseeing Mariko, heard her say that Saito told her that her true father did not want her, something Isobe knew was not the whole truth of the matter. Saito had in fact been vastly manipulative of Mariko's feelings while in isolation, leading to her arrogant presumption of control over Mariko. In the anime, her murder seems to be childish cruelty on the part of Mariko, and Saito's dying act vastly more heroic. It appears likely that it was Saito who made Mariko's genetic material available to Nousou.
Saito's Japanese voice actress, Maria Yamamoto, also acted as seiyu for Kisaragi and Kanae, giving her characters possibly the three most gruesomely memorable deaths in the entire anime series. The only exception to this is Aiko Takada.
In English, Allison Sumrall voices not only Saito but Aiko Takada and the Orphanage Girl. This circumstance makes her share a voice actress with Aiko in both dubs.