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In the pilot, the twins are reunited during a chance encounter shopping at a clothing store at the mall with their adoptive parents. The premise is similar to the movie The Parent Trap, in which a pair of separated-at-birth twins has a chance encounter at summer camp.

Tia Landry (Tia Mowry) is the intelligent twin from inner city Detroit, where her adoptive mother, Lisa (Jackée Harry), works as a seamstress; Tamera Campbell (Tamera Mowry) is the boy-crazy twin from the suburbs, where her adoptive father, Ray (Tim Reid), owns a successful limousine service. After their unexpected encounter in the department store, Ray reluctantly allows Tia and Lisa to move in the house because Lisa was about to take a job in St. Louis, which would have separated the girls. The girls' neighbor is a nerdy Roger Evans (Marques Houston), an annoying teenager who is infatuated with both of them, and who evolves into a perfect gentleman they both find attractive. In the final season when the girls go off to college, Roger disappears from the series without any explanation. By the fifth season, Tia and Tamera ended up with steady boyfriends: Tia with a boy named Tyreke Scott (RonReaco Lee) and Tamera with a boy named Jordan Bennett (Deon Richmond).

In the sixth season episode "Father's Day," the twins meet their biological father, Matt Sullivan, and learn that he is white and a famous photojournalist. Matt never married their mother, Racelle Gavin, because they never got the chance: she had been asked to paint a mural in Florida and he had been assigned "the opportunity of a lifetime" in the Middle East. Also, Racelle told him that she would later join him in Tel Aviv without telling him of her pregnancy. After six months, Racelle suddenly stopped writing. When the girls' mother died, Matt was not allowed to see them because he couldn't prove he was their father. When he searched for his twin daughters, he never found them because they had been adopted by two different people.

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