Rosemary explains that she is going to “skip the beginning” of her story and “start in the middle,” which takes her to the winter of 1996. It has been 10 years since she has last seen her brother (Lowell) and 17 since her sister (Fern) “disappeared.” Rosemary is 22 and in her fifth year of college at UC Davis. One day, she is having lunch in the cafeteria when she witnesses a fight between a girl, Harlow, and her boyfriend, Reg. Harlow screams and throws a chair at Reg, who calls her a “psycho bitch.” Officer Haddick and other members of the campus police arrive and mistakenly approach Rosemary, thinking she was involved in the fight. Rosemary throws her plate of food and glass of milk on the ground, and both she and Harlow are arrested.
The girls are taken to the county jail and placed in a cell. Reg comes to collect Harlow, and Rosemary is forced to call her father, who convinces Officer Hardick to drop all the charges against her in exchange for Rosemary promising to come home for Thanksgiving. Rosemary’s family live in Indiana, and they do not discuss her arrest or any other contentious matters during the holiday. They spend Thanksgiving with Rosemary’s maternal Grandma Donna, her Uncle Bob, Aunt Vivi, and cousins Peter and Janice. Rosemary’s mother’s family do not like Rosemary’s father, who is a psychologist and professor. As Rosemary is preparing to head back to California, her mother tells her that she was considering donating her journals to a library, but has decided to give them to Rosemary instead.
During the flight back to California, the airline loses Rosemary’s suitcase, which contain the journals. When Rosemary returns home, she is shocked to find Harlow in her apartment. Harlow explains that Reg kicked her out and she managed to persuade Rosemary’s building manager, Ezra Metzger, to let her in. Harlow offers to make it up to Rosemary by taking her out for a drink. At the bar, Rosemary tells Harlow about a time when she was “shipped off” to live with her paternal grandparents, Grandma Fredericka and Grandpa Joe. Rosemary ended up running away and attempting to walk all the way home to her parents’ house in Bloomington.
A few days later, Ezra hands over Rosemary’s suitcase, which the airline returned while she was out; he also tells her that her brother, “Travers,” came by and was looking for her. Rosemary finds it hard to believe that Lowell found her, but is convinced by the fact that he would not have used his real name. She realizes that the suitcase the airline returned is not actually hers.
The narrative jumps back to the year 1979. Rosemary is five years old and has just been picked up from Grandma Fredericka’s house after attempting to run away. She is taken to an unfamiliar house and is horrified to realize that a member of her family has been “given away.” Lowell is furious with their parents about Fern’s disappearance, but Rosemary is frightened and even relieved that she was not the one who was given away.
After Fern’s disappearance, Rosemary’s mother has a nervous breakdown and is no longer able to eat, talk, or leave her room. Rosemary is babysat by a college student named Melissa, who sits in front of the TV, allowing Rosemary to sneak out with Lowell and their neighbor Russell Tupman. Lowell and Russell drive to their old house and persuade Rosemary to help them break in. The house is empty and Rosemary feels that it is “sad” and “angry.”
At this point Rosemary explains that both her imaginary friend Mary and her sister Fern are chimpanzees. She did not reveal this detail until this point because she wanted the reader to see Fern as truly her sister. Rosemary recalls memories of the games she and Fern used to play, which would be assigned and monitored by graduate students in order to test and compare the sisters’ abilities.
Rosemary’s mother recovers from her breakdown and the family goes on vacation to Hawaii for Christmas. Rosemary’s father tells her that Fern has gone to live on a farm with a new family. The kids in Rosemary’s kindergarten class start to tease her, calling her “monkey girl.” Lowell, meanwhile, gets a counselor, Ms. Delancy, to help him process his grief over the loss of Fern. Lowell is made point guard of the high school basketball team, but one day Rosemary finds him at home when he is supposed to be at practice. That night, Lowell runs away from home and never returns. On his way, he frees all the lab rats from his father’s university laboratory. Some time later, the FBI arrive at the Cookes’ house and inform them that Lowell is a suspect in a fire that caused millions of dollars’ worth of damage to a veterinary laboratory at UC Davis.
One day, Rosemary is riding her bike in Bloomington when she runs into Lowell’s high school girlfriend Kitch Chalmers. Kitch tells her that on the day Lowell missed basketball practice, they had run into one of the graduate students who previously worked with Rosemary and Fern. The student explained that Fern had been taken to live with a large group of chimps at a lab in South Dakota run by a cruel professor who treated her badly. Lowell freaked out, exclaiming: “That’s my sister in that cage.”
At college, Rosemary’s freshman year roommate is named Larkin Rhodes, but insists that everyone call her Scully. Rosemary attempts to bond with Scully and other freshmen, but misreads social cues and ends up excluded from their friendship group. In her second year, she moves in with an art history major called Todd Donnelly.
Back in 1996, Rosemary realizes that she likes Harlow because of Harlow’s “monkey-girlishness.” Still stunned by Ezra’s mention of Lowell’s appearance, Rosemary researches the Animal Liberation Front, a radical animal rights organization she believes Lowell has been working with during his years of absence. Harlow persuades Rosemary to open the suitcase the airline mistakenly gave her, and they find a ventriloquist’s dummy inside who Rosemary calls Madame Defarge.
Rosemary is sitting in lecture for a course entitled Religion and Violence. The professor, Dr. Sosa, explains that, like humans, chimpanzees commit intra-group violence. He begins talking about the issue of rape among chimps and this causes Rosemary to have a panic attack. After the lecture, Rosemary meets Harlow at a restaurant with the aim of getting drunk. Reg is there too, as is Madame Defarge. Rosemary takes a couple of pills that Harlow gives her and quickly begins thinking and behaving in a strange way. The night proceeds chaotically, and suddenly Rosemary bumps into Lowell. However, at that moment Rosemary is again arrested by Officer Haddick and placed in a cell with Harlow. Harlow complains that Rosemary talks all night, but Rosemary is not even aware of this and cannot stop herself. After being released, she realizes that she’s lost her bicycle and also Madame Defarge.
The next day Rosemary leaves the apartment; on her return Todd and his girlfriend Kimmy say that while she was out, a man came to return Madame Defarge, Harlow showed up, and finally Rosemary’s brother “Travers” arrived. Harlow and Lowell left together to get dinner, asking Todd to invite Rosemary to join them. Rosemary walks to the restaurant and finds Harlow and Lowell. She feels annoyed that Harlow is taking Lowell’s attention. Later that night, Lowell comes to Rosemary’s apartment, wakes her and takes her to a diner. They stay there talking all night. Lowell explains his involvement in activism against animal abuse. He tells Rosemary horrifying stories about animal suffering, and says that he tried to rescue Fern multiple times from the lab in South Dakota. However, now that he is on the run from the FBI he cannot keep trying, and he assigns the role of looking after Fern to Rosemary.
Rosemary walks Lowell to the train station, wishing he would stay longer. They part, and Rosemary returns home. She falls asleep holding Madame Defarge. A few days later, she writes about the topic of animal abuse in her Religion and Violence final, and is reprimanded by Dr. Sosa for failing to answer the question.
During their one day of knowing each other, Harlow fell in love with Lowell, and is miserable now that he is gone. This annoys Rosemary, and she tries to avoid Harlow. Rosemary is packing to return home for the Christmas vacation when the police arrive at her door and take her in for interrogation. They ask if she is Lowell’s sister, but she refuses to answer any more questions until a lawyer is present. The interrogation is abruptly ended, and Kimmy, Todd, and Todd’s mother—a famous civil rights lawyer—are waiting to pick Rosemary up. They explain that Ezra has been arrested for breaking into the UC Davis Primate Center and attempting to free the monkeys. Harlow has been named as his accomplice, but she has managed to escape. When Rosemary returns home, she finds that Madame Defarge is gone.
Rosemary goes home for Christmas and eventually tells her parents about her encounter with Lowell. The family finally confronts the matter of Fern’s absence, and Rosemary’s parents explain that much of what she remembers of that period is incorrect. They explain that Rosemary should not blame herself for Fern’s disappearance, and that they were in fact forced to give up Fern because as she got older she was too dangerous to keep in the house.
Todd’s mother helps Ezra to get the fairly light sentence of eight months in a minimum- security prison. Harlow is still on the run. Rosemary and Reg begin dating, but break up after five months. In 1998, Rosemary’s father dies after a series of heart attacks at the age of 58. Meanwhile, Rosemary and her mother work on preparing her mother’s journals for publication. In 2012, they are living together in Vermilion, South Dakota, near the lab where Fern is kept along with her daughter, Hazel. Rosemary is a kindergarten teacher and her mother volunteers at Fern’s lab. The book based on Rosemary’s mother’s journals is about to be published. Rosemary’s agent calls to inform her that she has received an influx of requests for interviews; the reason why is that Lowell has finally been captured, just as he was planning an attack on SeaWorld Orlando. Harlow remains at large.
Rosemary explains that she decided to write the book the reader is holding “for Lowell.” She ends the story by describing what happened when she and Fern saw each other for the first time again in South Dakota. Rosemary signed her name and Fern’s name, and Fern came over and pressed her hand, and then her forehead, against the glass separating them. Rosemary couldn’t know what Fern was thinking, but she still felt that it was like looking in a mirror.