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Sixteen-year-old homeschooled Cady Heron and her zoologist parents return to the United States after a twelve-year research trip in Africa, settling down in Evanston, Illinois.Attending a public school for the first time, Cady meets new classmates Janis Ian and Damian Leigh.Despite this discovery, Cady decides to forego Janis's scheme for ethical reasons.Meanwhile, Cady becomes attracted to Regina's ex-boyfriend, Aaron Samuels, whom a jealous Regina proceeds to steal back at a Halloween party by kissing him in front of Cady.As part of her punishment for lying and failing Ms.Norbury's class, she joins the Mathletes in the state championship finals, and ends up winning the competition for her team after her opponent answers incorrectly.Without any friends, shunned by Aaron, grounded by her parents and despised by her peers at school, Cady takes full blame for the Burn Book and becomes an outcast.
Rachel Mc Adams was cast as Regina because Fey felt Mc Adams being "kind and polite" made her perfect for such an evil-spirited character.
When Regina is finally made aware of Cady's treachery, she retaliates by spreading the contents of her Burn Book all over the school, quickly inciting a massive brawl.
To avoid suspicion, Regina inserts a fake libel of herself in the book in order to blame Cady, Gretchen, and Karen, the only female students not mentioned in the book.
Regina has joined the lacrosse team to deal with her anger, Karen has become the school weather reporter (claiming that her breasts can tell when it is raining), and Gretchen joins the "Cool Asians".
Aaron graduates from high school and attends Northwestern University, Janis begins dating Mathlete Kevin Gnapoor, whom she initially despised, and Cady declares that she is now normal.
The real Janis Ian was one of the musical guests on the first Saturday Night Live episode, in which she sang the song "At Seventeen", which can be heard playing in the background when the girls are fighting at Regina's house.