Plot

Continuing from the end of "The End of Time, Part 2", the newly regenerated Doctor crash-lands his damaged TARDIS in Leadworth, in 1996. He meets seven-year-old Amelia Pond. While waiting for the TARDIS to self-repair, he explores his new face, and discovers that while he has a distaste for many foods, his new body likes the taste of "fish custard" (a dish he invented which consists of fish fingers and custard). Amelia then shows the Doctor a scary crack in her bedroom wall. The Doctor discovers it is a crack in time and space itself, briefly opening it to discover an Atraxi prison. The Atraxi send a psychic message to the Doctor that "Prisoner Zero has escaped". Then the TARDIS's cloister bell is heard; the Doctor races back to his machine, needing to travel in time to prevent its systems from overheating, and promises Amelia that he will return in five minutes. Amelia hastily packs a suitcase and waits near where the TARDIS had previously landed.

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The Doctor lands the TARDIS outside Amelia's house, unaware 12 years have passed. On searching the house, he is knocked out and wakes up handcuffed and without his sonic screwdriver. He discovers his assailant is a much older Amelia, now going by the name Amy. Her fascination in waiting for his return led her to create toys and stories about him, and she was ridiculed by other villagers. The Doctor then reveals to Amy that Prisoner Zero has been hiding in a room in her house that she had never noticed, due to a perception filter. After venturing into the room, she frees the Doctor and grants him his sonic screwdriver. They dodge an attack by Prisoner Zero and flee the house.

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Shortly afterwards, the Atraxi arrive in orbit, alerted by the Doctor's arrival, and issue an ultimatum: if Prisoner Zero does not "vacate the human residence", meaning the Earth, "the human residence will be incinerated". Meeting Amy's boyfriend Rory, the Doctor realises that Prisoner Zero, a multiform that can take the form of any unconscious being by forming a telepathic link with them, is borrowing the forms of a nearby hospital's coma patients. The Doctor uses a laptop to gatecrash an online meeting of scientific experts discussing the Atraxi situation and send instructions to them.

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The Doctor races to the hospital, just in time to save Amy and Rory from Prisoner Zero. The Doctor reveals his plan: he has created a computer virus that will broadcast the number "zero" across the world. It is tied to Rory's phone, which contains images of the coma patients, identifying Prisoner Zero in whatever form it may take. Prisoner Zero reveals it has one more form that is not on Rory's phone. Prisoner Zero knocks out Amy and transforms into the Doctor and young Amelia, whom he was able to link with during the years of the Doctor's absence. The Doctor realises that Amy can hear him speaking and manipulates her subconscious to remember the form of Prisoner Zero she had seen in her house. This forces Prisoner Zero to revert to his true form; it is identified by the Atraxi and captured. Before being transported away, Prisoner Zero warns the Doctor that "Silence, Doctor ... silence will fall." The Atraxi fleet leaves, but the Doctor, invoking the Shadow Proclamation, orders their return and reprimands them for threatening the planet. The Doctor shows the Atraxi images of the many past alien invaders who have attempted to seize or destroy the Earth, but who have been defeated by his past incarnations, causing the Atraxi to take him at his word, and "run."

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The Doctor finds the TARDIS and departs before Amy or Rory can catch up. The Doctor later returns to Amy's house, finding that another two years have passed. Though Amy is still upset, she readily accepts his offer to travel together, as long as he can return her the next day. In response to why he chose her, he declares that he is lonely, although he is shown analyzing the crack and possibly wants to monitor his new companion. As the TARDIS dematerialises, the viewer is shown Amy's bedroom, where, alongside her toys and drawings of the "raggedy Doctor," lies her wedding dress.