Cal/lie Stephanides was first born as a girl in Detroit in 1960, and then born again as a teenage boy in Petoskey, Michigan, in 1974. He is intersex, and is now 41 years old and living in Germany. He has decided to write his memoir after reading about historical figures who were also intersex. Cal’s grandmother, Desdemona, was born in Bithynios, a small village on Mount Olympus near Bursa in Asia Minor. Both her parents died in World War I, leaving her and brother, Lefty, as orphans. Desdemona works in a silkworm cocoonery. In 1922, Desdemona tries to set Lefty up to marry girls in their village, but Lefty isn’t interested. Despite the fact that they are brother and sister, Desdemona and Lefty are secretly in love with each other.
After years of Greek rule, the Turks reinvade the area of Asia Minor where Lefty and Desdemona live, and they plan to flee to the U.S. via Smyrna. Desdemona secretly brings her silkworm box with her, despite Lefty’s insistence that no one in America farms silk. In Smyrna, Lefty briefly encounters a young Armenian doctor named Dr. Philobosian, whose entire family is soon slaughtered in the Turkish assault on the city. It becomes increasingly clear that the whole city is about to be destroyed and on-Turkish residents killed. Convinced that they are about to die, Desdemona agrees to marry Lefty. However, at the last moment they are able to escape by pretending to be French citizens. They bring Dr. Philobosian with them. Onboard the ship to the U.S., Lefty and Desdemona pretend to be strangers and engage in a fake courtship, followed by a wedding.
In the U.S., they are greeted by their cousin, Sourmelina, who moved to the U.S. years before and has completely assimilated. They trust Sourmelina to keep the secret that they are brother and sister because Sourmelina herself also has a secret: she is a closeted lesbian. Lefty and Desdemona go to live with Sourmelina and her husband, Jimmy Zizmo. Lefty gets a job as a factory worker at the Ford Motor Company and learns English at night. However, the same day he graduates from his English course, he is told that he has been fired for living with someone (Zizmo) who has a criminal record. On this same night, Sourmelina and Desdemona tell their husbands that they are both pregnant, having conceived at the exact same moment.
Now that Lefty is unemployed, he starts working with Zizmo in the bootlegging business during Prohibition. Sourmelina gives birth to a daughter named Theodora (Tessie). While Desdemona is giving birth to her son, Milton, Zizmo attempts to drive himself and Lefty over a frozen lake to Canada for a “final scheme.” However, Zizmo he drives his car into the ice and drowns, while Lefty gets out just in time. After Theodora’s birth, finding himself once again without a job, Lefty opens a speakeasy in his basement called the Zebra Room. He also tells Desdemona to get a job, and after seeing an ad in the newspaper for a silk worker, she goes to inquire about the job, only to find herself in the Black Bottom ghetto. To her surprise, the address in the ad is for a mosque run by the Nation of Islam. Desdemona starts working there, teaching the young followers of the movement how to make silk and showing them her silkworm box. While working, she listens to speeches made by the movement’s leader, Minister Fard, and is forced to confront her own complicity in racism as a white person. When a scandal forces Fard to leave Detroit, he reveals to Desdemona that he is really Jimmy Zizmo (and that he faked his own death).
The narrative jumps forward to World War II, when Milton and Tessie are young adults. Desdemona has noticed an intimacy developing between them, which brings back her fears about her own incestuous relationship. Milton ends up seducing Tessie by blowing his clarinet on different parts of her body. However, Tessie then gets engaged to a young man named Michael Antoniou, who is training to be a priest. Furious, Milton enlists in the Navy. Desdemona is beside herself with worry about Milton’s safety, and although won’t admit it, so is Tessie. Eventually, Tessie decides that she can’t marry Mike, and calls of the engagement, accepting Milton’s offer instead. Mike ends up marrying Milton’s younger sister, Zoë. Milton and Tessie have a son, Chapter Eleven. Milton takes over the Zebra Room, and without anything else to do, Lefty starts gambling and spends all his and Desdemona’s money, forcing them to move in with Milton and Tessie. Callie is conceived when Chapter Eleven is about five, and she inherits two copies of a recessive gene, which causes intersex conditions, that has been in her family for over 200 years. On the day Callie is born, Lefty has a stroke and loses his ability to speak.
When Callie is seven years old, the 1967 Detroit Riot erupts, and while most of the Stephanides family spend their time hiding in the attic, Milton spends the period crouched inside the Zebra Room, holding a gun. Fearing for her father’s life, Callie sneaks out to save him on her bike. A man throws a Molotov cocktail into the Zebra Room, although by this point Milton and Callie are safe. The insurance payout is large, and allows the Stephanides family to buy a Cadillac and move to the affluent suburb of Grosse Pointe, where they live in a strange house on a street called Middlesex Boulevard. Callie befriends her neighbor, a little girl called Clementine, and the two girls begin to sexually experiment together. However, then Clementine’s father dies, and she and her mother move away. At the same time, Lefty has another stroke. His mind deteriorates, to the point that he forgets whole periods of his life and thinks he is living in another era. He reveals the secret that he and Desdemona are brother and sister, but no one in the family believes him, assuming he is speaking nonsense. Eventually, he dies. Despondent, Desdemona gets into bed with the plan of never getting out again. She remains there for 10 years.
Later on, Milton opens a chain of hot dog restaurants called Hercules Hot Dogs. At 12 years old, Callie notices that other girls her age have grown breasts and started their periods, and is concerned that this hasn’t happened to her. She now attends the private Baker & Inglis School for Girls, where she is socially excluded due to her class background and Greek ethnic identity. Chapter Eleven comes home from college a totally transformed person; having embraced countercultural style and ideology, he has grown his hair long, drives a motorbike, and has started meditating and taking acid. Meanwhile, in Mr. da Silva’s advanced English class, Callie develops a crush on her classmate, whom she nicknames the Obscure Object. When the two girls are cast in a production of Antigone, they develop a friendship.
Just as the first (and only) performance of Antigone is due to begin, another girl in Callie’s class, Hettie Grossinger, collapses onstage from a brain aneurism and dies. Over the summer, Callie and the Obscure Object become inseparable. Callie meets the Object’s brother, Jerome, whom she finds annoying. Callie and her family are supposed to go on a trip back to their ancestral village of Bithynios, but the Turkish invasion of Cyprus prevents this from happening, and Callie goes to the Object’s summer house in Petoskey instead. There, Callie gets drunk and high on marijuana and has sex with Jerome while the Object hooks up with Jerome’s friend, Rex Reese. However, shortly after this Callie and the Object start having sex themselves, although they do not verbally acknowledge that this is happening. Callie notices that her genitals look different from the Objects’, but this doesn’t particularly bother her.
Soon after, Jerome catches the girls having sex on the porch, and accuses them of being “Carpet munchers.” Callie punches him and spits in his face, and while running away gets hit by a tractor. The Obscure Object rushes Callie to hospital, and on the way they kiss. However, this is the last time they will ever see each other. In hospital, the doctors are shocked to find that Callie is intersex. She is sent to New York to a see a famous sexologist, Dr. Luce, who specializes in intersex conditions. While staying in New York for Callie’s examination, Milton and Tessie try to pretend like they are having a fun vacation, but Callie is miserable. After learning that she is actually more biologically male than female, but that Dr. Luce wants to give her hormones and surgery to confirm a female identity, Callie decides to run away and assume a male gender identity, changing his name to Cal.
Cal hitchhikes across the country, cutting his hair short and acquiring men’s clothes en route. He is picked by various shady people, including a man who tries to have sex with him named Ben Scheer and another man named Bob Presto. In San Francisco, Cal lives in a park with a group of young homeless Deadheads. After he runs out of money and is beaten up by two homeless men who discover he used to have female gender identity, Cal calls Bob for help. Back in Detroit, Milton and Tessie are distraught at Cal’s ongoing absence. They try everything they can to find him (although at this point they still think of him as “her”), to no avail. One day, Milton gets a phone call from someone claiming to have kidnapped Cal and asking for a ransom of $25,000. Milton agrees to pay it immediately. In San Francisco, Cal ends up performing as “the god Hermaphroditus” at Bob’s sex club, Sixty-Niners. He performs alongside an intersex person named Zora and a trans woman named Carmen. Cal lives with Zora, and from her gains knowledge and appreciation about intersex people. Zora is proud of her condition and writing a book called The Sacred Hermaphrodite. One night, Sixty-Niners is raided by police, and Cal is arrested.
Without telling anyone what he is doing, Milton drives to the agreed upon place to deliver the ransom money, and is shocked to find that the “kidnapper” is Father Mike. A car chase ensues, and Milton realizes that Mike robbed him and is planning to flee to Canada. Mike makes it over the Canadian border, and while trying to follow him Milton ends up driving off a bridge and into the Detroit River. Chapter Eleven comes to pick Cal up from jail in San Francisco and is surprisingly accepting of Cal’s new identity. The brothers fly back to Detroit together. Cal reunites with Tessie and also Desdemona, who remains bedridden. Desdemona is now also senile, and initially thinks Cal is Lefty when she sees him. When Cal explains that he is intersex and transgender, Desdemona reveals the secret that she and Lefty were brother and sister. While Tessie and Chapter Eleven go to Milton’s funeral, Cal decides to stay and guard the door of the house to stop Milton’s spirit reentering, a Greek tradition performed by a male relative of the deceased.
