The novel starts with a narration by its protagonist, Cal (his masculine identity), also known as Calliope (feminine): He recounts how 5-alpha-reductase deficiency, a recessive condition, causes him to be born with female characteristics. The book continues with accounts of his family's history, starting with his paternal grandparents in their home village and ending with his father's funeral. These accounts cover the conception of Cal, his teenage years, and the discovery of his intersex condition. Throughout the book, Cal weaves his opinion of the events in hindsight and of his life after his father's funeral. Eugenides sets Middlesex in the 20th century and interjects historical elements, such as the Balkan Wars, the Nation of Islam, the Watergate scandal, and the 1967 Detroit riot in the story. is an American novelist and short story writer. He has written numerous short stories and essays, as well as three novels: The Virgin Suicides (1993), Middlesex (2002), and The Marriage Plot (2011). The Virgin Suicides has been filmed, while Middlesex received the 2003 Pulitzer Prize for Fiction in addition to being a finalist for the National Book Critics Circle Award, the International Dublin Literary Award, and France's Prix Médicis.
Eugenides is now based, with his wife and child, in Princeton, New Jersey, where he is Professor of Creative Writing in the Peter B. Lewis Center for the Arts. Of teaching creative writing, Eugenides remarked in an interview in The Paris Review, "I tell my students that when you write, you should pretend you're writing the best letter you ever wrote to the smartest friend you have. That way, you'll never dumb things down. You won't have to explain things that don't need explaining. You'll assume an intimacy and a natural shorthand, which is good because readers are smart and don't wish to be condescended to. I think about the reader. I care about the reader. Not 'audience.' Not 'readership.' Just the reader."