The Doctor takes him into the TARDIS where tells Rory and Amy that he has come to save their relationship and that he is taking them to Venice as a wedding present. Rory is distinctly unimpressed by the TARDIS. When they enter the city they find that it is under quarantine because of a plague. The quarantine order is signed by Signora Calvierri. The Doctor uses his psychic paper to gain entry.
They see Guido trying to attract Isabella's attention as she exits the school with other girls. All wear white dresses with veils over their faces and carry parasols. Isabella does not respond to him and another of the girls bares her fangs. Intrigued, the Doctor approaches Guido to find out why he is trying to get his daughter back and who the girls are. Guido says that something magical happens in the school. The Doctor decides to see Calvierri.
Rosanna Calvierri is 'hydrating' (drinking copious amounts of water) when Francesco tells her that the time has come to introduce the girls to his brothers. She tells him that they will follow the plan. Amy and Rory catch up on what she has been doing without him. He is just beginning to get excited by where and when they are when they see Francesco attack a flower girl in the streets and drink some of her blood. Amy follows him while Rory checks on the girl.
Guido tries to see Isabella by shouting at the gate but it s a diversion to allow the Doctor to sneak in by a side gate. Inside, he is accosted by five of the girls at the school. They speak in unison, have fangs and no reflection. He makes a quick exit and meets Amy. They excitedly swap stories of vampires.
They go to find Guido who tells them there is a trapdoor into the school but they need to have somebody on the inside. Amy suggests that Rory poses as her brother to get her in to open the trap door beneath the building. Guido has another plan involving gunpowder but the Doctor vetoes it. The Doctor wonders what is so bad that the Calvierris would rather people think they are vampires.
Amy is accepted after Rory introduces himself as a 'gondola driver'. Really, it is because Signora Calvierri is intrigued by their use of psychic paper to show their reference from the king of Sweden. Amy meets Isabella who tells her that she is taken at night to a room where she thinks surgery is performed on her.
The Doctor, Rory and Guido use Guido's gondola to access an underground canal that brings them to the trapdoor. Amy finds and unlocks the trap door, but is captured and taken to the room that Isabella told her about. Rosanna reveals that she recognised the psychic paper and questions her. Amy replies that she is from Ofsted so Rosanna bites her neck.
The Doctor and Rory find a body which has had all the moisture taken out of it. Franceso wants to drink from her. Rosanna tells Amy that the vampires drink girls dry, then fill them with their own blood. They will either die or transform. There are ten thousand husbands waiting for her in the water. Amy says that she is already engaged and kicks out at Rosanna. Her foot connects with a device on her hip and Rosanna reverts to her real form: an alien fish with spiny fingers. The Doctor and Rory approach via a corridor. All of the 'vampires' turn to chase them off and Isabella frees Amy. The Doctor holds the 'vampires' at bay with an ultra-violet light while Isabella leads her rescuers to the door. The others pass outside but Isabella is stopped by the sunlight and recaptured. The Doctor tries to get in to save her but the door is electrified and he fails.
Isabella is fed to her 'husbands' as a traitor in memory of all of those who were lost to the Silence by being pushed into the canal.
Rosanna re-enters the house to find the Doctor waiting on her throne. She realises that he must be the owner of the psychic paper and he tells her that she is from Saturnyne and using a perception filter to appear human. He says that they have no reflection as the brain is unable to compute a reflection that is different from the real world image and so blocks the image out. Rosanna adds that self-preservation allows people to see the fangs. Rosanna tells him that cracks appeared in the universe and her planet was lost so they found an ocean like her own. She asks the Doctor's aid in creating a colony on Earth but he refuses because she didn't know Isabella's name. She allows him to leave before calling her household to her and telling them that "the storm is coming." As she descends the stairs her perception filter malfunctions and her shape fluctuates between alien and human
In Guido's house the Doctor sonics Amy's neck wound and pronounces her fine before popping a sweet into her mouth. He talks over the possible plans that Rosanna may have and concludes that she intends to sink Venice and repopulate it with the transformed girls and her sons. He guesses that only male children survived the journey through space.
When the house is attacked by the vampire girls (or "fish from space" as the Doctor calls them, adding that "fish from space have never been so...buxom") the Doctor and his companions escape but Guido lights the gunpowder he has stored in the cellar. He kills himself the girls.
Rosanna switches on her machinery to initiate a storm over Venice. The Doctor tells Amy and Rory to return to the TARDIS while he goes back to the Calvierri house to find the device. While he is there he tells Rosanna that the girls are gone. She leaves, telling him that it is up to him to save the 200,000 residents of Venice. Meanwhile, Francesco goes after Amy and Rory. Rory taunts him with being uglier than his mother to get him away from Amy. She kills Francesco by shining sunlight on him with her mirror. They decide to go back to help the Doctor.
He gets them to rip out the wiring from Rosanna's throne so that the control defaults to the device at the top of the tower. He then climbs up the Calvierri's tower and deactivates the weather device. Sunlight breaks out. Rosanna goes to the canal in her human guise. The Doctor tries to stop her but she jumps in and is devoured by her sons.
Amy invites Rory to travel with her and the Doctor in the TARDIS. The Doctor says that it is fine by him and Rory is delighted to accept. As he and the Doctor enter the TARDIS silence falls across the city.