In Venice, 1580, a boat builder, Guido, comes before Senora Rosanna Calvierri and asks for permission to enroll his daughter Isabella and give her a future. Rosanna understands the value of protecting the future of one's family and agrees to take her on as a student. However, she tells the father that she will accept Isabella immediately, and she must make her goodbyes. The boat builder is escorted out and Rosanna and her son Francesco inspect Isabella, and Francesco opens his mouth to bare his fangs.
At a pub, Rory and his mates are having his stag party on the night before his wedding. Rory calls Amy at home and leaves a message that he loves her. The cake arrives and the Doctor bursts out. He informs Rory that they need to talk about his fiancée, and that she tried to kiss him, but she's a great kisser. The partygoers are not amused.
Later, the Doctor is working on the TARDIS and talking to Rory and Amy. He's decided to send them together to somewhere amazing. When Rory isn't impressed with the TARDIS' vast interior, the Doctor takes offense, and then decides to take them to Venice in 1580. They run into an inspector, who demands to see their papers. Thanks to the Doctor's psychic paper, he takes the Doctor for a high-ranking church official. While Rory takes the psychic paper to figure out how it works, the inspector explains that he's checking for plague and the city is quarantined thanks to the wisdom of Lady Rosanna. When the Doctor notes that the plague died out years ago, the inspector explains that Rosanna has said she's seen the plague in other cities.
Rosanna's students, all female, don their veils and leave the school. Guido rush to them and pulls off their veils, trying to find Isabella. They hiss at him and one of them bares fangs. When Guido finds Isabella, she doesn't seem to recognize him. Francesco informs him that Isabella is gone and leads the students away. The Doctor, Rory, and Amy notice the exchange, and the Doctor goes to see Guido for an explanation. He wonders why Guido is trying to get his daughter out, and Guido warns that something magical happens to the students once they go in. The Doctor decides to see Senora Rosanna.
Francesco comes to see his mother as she hydrates in her courtyard. He explains what happened, and suggests that they've converted enough women and it's time to introduce them to his brothers. Rosanna says that she will decide when she has enough, and tells him to let the locals continue to beg them to accept their daughters. The bell chimes and Rosanna leaves.
As they walk the streets, Rory asks if Amy has missed him. She insists that they focus on their date and he decides to enjoy their experience. As they continue, they walk past Francesco, who approaches a flower girl. A few seconds later, Amy and Rory hear a scream. They come back to find Francesco draining blood from the girl's neck. He quickly leaves and Amy goes in pursuit before Rory can stop her. She follows him to the canals but loses him, unaware that Francesco is in the water below.
While Guido goes to the gates of the school and creates a distraction, the Doctor slips around to a side gate and goes inside. As he checks himself in the mirror, he sees nothing behind him. However, when he turns he discovers that the female students are there, but cast no reflection. The Doctor is impressed at their magic trick, and they ask who he is. He shows them his psychic paper but pulls out his library card after realizing Rory took his paper earlier. He realizes that they are vampires but wonders why they want to shut down the city. They bare their fangs and close in on him, and the Doctor hastily runs outside. He runs into Amy, and they both realize they're dealing with vampires. Rory isn't quite so thrilled.
The Doctor takes them to Guido, who shows them plans and reveals that there is a tunnel beneath that leads inside. There is a trapdoor blocking the entrance, and Amy suggests she sneak inside. Both the Doctor and Rory refuse to let her endanger herself. The Doctor notices that Guido has gunpowder stored away, but doesn't want to use weapons. The Doctor finally agrees to let Amy go inside, and they try to figure out a way to get her inside. Amy suggests that since the Calvierris have seen the Doctor, that Rory pretend to be her brother and take her inside. When Rory worries that they're up against vampires, the Doctor wonders if they're up against something worse.
Rory takes Amy to the Calvierri court, but Francesco vaguely remembers Amy from when he saw her after he attacked the girl. Rosanna wonders why Rory has been allowed in, and her steward explains that they have references from the King of Sweden. Rory shows her the Doctor's psychic paper while Francesco continues to inspect Amy. Rosanna accepts Amy immediately and has Rory escorted out, as Francesco starts to bare his fangs. The steward then takes Amy to the bed chambers and orders her to get changed. The other girls examine her and leave, and Amy finds Isabella in the next bed. Amy promises to get her out and asks for an explanation, and Isabella tells her that the others take her to a room with a green light and strap her into a chair. Then she blanks out until the next day, and the sunlight burns her skin.
Guido, Rory, and the Doctor take a gondola to the tunnels beneath the Calvierri school. Amy enters the basement, finds the trapdoor, and opens it. However, the steward finds her.
As they enter through the tunnels, the Doctor tries to explain about the kiss and dismisses it as her relief. Meanwhile, the steward brings Amy to the green room. Rosanna is waiting, and notes that psychic paper doesn't work on her.
The Doctor and Rory come up through the trapdoor but find no trace of Amy. They start to search, the Doctor using a UV flashlight.
Rosanna demands to know where Amy has come from and how she has psychic paper. They bring out the chair and rig up blood bags, and then strap Amy in. Rosanna bears her fangs and bites her in the neck.
As Rory worries about canceling the wedding, the Doctor finds a trunk filled with dehydrated corpses.
After Rosanna has fed on Amy, Francesco asks to share. His mother grants him permission to feed.
The Doctor explains that the corpses have been stripped of their water, and concludes they are the ones who didn't survive the process. Realizing the danger that Amy is in, Rory points out that the Doctor endangers his companions by encouraging them to impress him. They're interrupted when the female students arrive. The Doctor holds them off with his UV flashlight.
Rosanna explains to Amy that they will drain her dry and then fill her with their blood. It will change her or kill her. If she survives, there are 10,000 husbands waiting for her in the water. Amy kicks Rosanna in the side, smashing her perception filter. When it shuts down, a fish-like alien is briefly revealed. Before she can do anything, the Doctor and Rory arrive. Isabella sneaks in and frees Amy, and the Doctor holds off the vampires long enough for them to get away to the basement. They get outside as the sun rises, but Isabella is forced to retreat back inside when the light burns her. When the Doctor tries to go after her, the electrified door shocks him unconscious.
Later, the steward presides over Isabella's execution as a traitor. They force her into the water and something pulls her under, biting at her legs. Rosanna then walks to the water's edge and Francesco warns her to change her form so his "brothers" don't mistake her for prey. She assures the creatures below that it won't be long.
When Rosanna returns to her court, she finds the Doctor waiting for her. She realizes that he's the owner of the psychic paper and assumes that he's a refugee like her. He offers a trade of information, and explains that they don't appear in a mirror because the perception filter can't handle the reflection. She admits that the target's self-preservation instinct overrides the filter, letting them see the fangs. In return, Rosanna asks where the Doctor is from. When he identifies himself as a Time Lord, he asks why she is here. Rosanna explains that her people ran from the Silence, the end of all things that they saw through the cracks in time. They fled to an ocean world, Earth, and the crack closed behind them. She wants to build a new society there and asks the Doctor to join them, In response, he asks where Isabella is. She proudly admits she executed Isabella as a daughter and will bend the heavens to save her race, and asks the Doctor for an answer. When he refuses, she has the steward escort him out.
Once the Doctor has left, Rosanna tells her people that the storm is coming. Her perception filter briefly shuts off and Rosanna realizes that it was damaged by Amy's attack. She then tells Francesco to prepare the girls.
The Doctor uses the sonic screwdriver to heal Amy's neck wound, and then tries to come up with an idea. He realizes that Rosanna plans to do something to make the city hospitable to her people. Remembering what she said about bending the heavens, he realizes she's going to sink Venice. Amy remembers what Rosanna said about having 10,000 husbands in the canals. The Doctor concludes that only the male offspring survived the journey, and Rosanna is creating females to breed with them. They hear a commotion upstairs and Guido explains that there's nobody upstairs. The students break in and the Doctor holds them off with the UV flashlight, and then disrupts their perception filter with his sonic screwdriver. They retreat downstairs and Guido takes the UV light, and then closes the door and holds off the female students long enough to detonate the gunpowder, sacrificing himself to kill the students.
At the school, Rosanna activates a device that creates a massive storm.
The Doctor orders Amy back to the TARDIS, and she angrily walks away. Rory thanks the Doctor and goes with her. Francesco spots them, removes his cloak, and dives into the water in pursuit.
The Doctor returns to the school and examine the technology hidden in Rosanna's throne. Rosanna returns, impressed at his determination to save the city, and he tells her that the girls are dead. He asks for her help to save the Venetians but she walks away.
Francesco corners Rory and Amy, and is unimpressed when Rory tries to use a cross against him. The alien closes in on Amy but Rory finally gets his attention by insulting Rosanna. Rory tries to hold him off with a broom, and Francesco draws his sword. In the fight, Rory loses his broom but entangles Francesco briefly in some sheets. As he tries to get away, Francesco reverts to his true form and leaps at Rory, but Amy uses a mirror to reflect sunlight on him, causing him to explode. She then kisses Rory and tells her they need to help the Doctor. Shocked, Rory goes after her.
The Doctor ascends the school's belltower as the storm rolls in. As the rain starts to pour and the steward tries to escape stolen gold, Amy and Rory come in and Rory refuses to leave. The Doctor is angry that now he doesn't want to leave, but an earthquake shakes Venice. He tells them to worry about the tidal waves, and then tells them to pull all the wiring out of the throne, the device's control system. That will reroute control to the generator. Once the Doctor finds it at the base of the tower, he locates the main power cable and climbs up the outside to the top. Amy and Rory watch as the Doctor opens the device and shuts it down, dissipating the storm clouds and ending the rain.
On the docks, Rosanna discovers that her perception filter is giving out. She undresses and prepares to jump into the water. The Doctor arrives and she asks if one city was worth the sacrifice to save her people. He tells her that you can't go back in time, and she has to learn to mourn. Rosanna asks him to remember her and her race , and to dream of them, and then throws herself into the water in her human form. Her children consume her.
As they return to the TARDIS, Amy invites Rory to stay with them for a bit. He accepts and she goes into the TARDIS. As they go, the Doctor notices a sudden hush that falls across the town. As they leave, the Doctor remembers what Rosanna said about cracks.