Seventeen-year-old Madeline Whittier believes that she has a rare autoimmune disease called severe combined immunodeficiency, or SCID, which causes the body to have allergic reactions to several substances. Her mother Pauline, a physician, keeps Madeline confined in their house to avoid exposure to harmful substances outside. This confinement began when Madeline was an infant and almost died from an infection. A section of illustrated pages reveal that Madeline’s mother Pauline is her official medical caretaker and that detailed daily logs (updated almost hourly) are taken of Madeline’s breaths per minute, the room temperature, and the status of the room’s air filter. The logs’ data reveal that all the conditions are stable and normal.

Madeline describes her bedroom, which is painted and furnished white to ensure sterility, and how she writes fanciful rewards on the insides of her books if they’re lost and returned to her. These rewards include going on a picnic with her, snorkeling, walking down the block, etc. Madeline chooses these rewards because they are things she longs to do but isn’t allowed to because of her alleged autoimmune disorder. She alludes to the fact that it’s impossible for the books to be lost and returned because of her isolation.