The story begins at the conclusion of the previous novel The Twelve. The twelve and their followers have been destroyed, but Subject Zero is still hiding somewhere in America. Alicia Donadio gives birth to a stillborn child, the product of her rape in the previous book. Numbed by the pain of losing her child, she takes two years to heal before resuming her quest to find Subject Zero, the first "viral" human or one who has been infected.
About the same time, Michael Fisher is sailing across the globe looking for a haven at which to land. In the Gulf of Mexico he commandeers an abandoned ship in the hopes of taking some refugees with him to a supposed safe zone somewhere in the Atlantic Ocean. Apparently the virus has spread to Europe already. He encounters Lucius Greer, the caretaker of Amy, the prophesied deliverer, and learns that the virals are planning a resurgence, making his disembarkation even more urgent. Lucius has been taking care of Amy and Carter by feeding them daily in the hold of his own ship. They're both failing to the virus, but they exist in a dream state of bliss in their own imaginations.
Peter Jaxon as resigned from the military in order to raise his nephew, Caleb. They live in Kerrvile which is now the capital city of the Republic of Texas. He takes a job working for the new president and heads up a movement to reopen the gates. After years of quarantine, they believe the virals have all left for good by now. During all of this, Peter continues to have dreams about Amy. He builds an entire life with her in his dreams, only to finally admit that he loves her. Sadly he has no idea what's happened to her.
Alicia finally is successful when she tracks down Zero in New York City. He is protected by the viral which infected her, she is incapable of killing him. Since she has no other choice, she listens to his story. Zero's name was Tim Fanning. in college he fell in love with this girl Liz who liked him back, but they moved slowly. Liz discovered that she had cancer, after which Tim begged her to move with him overseas to live out the rest of her life in peace. When she doesn't make it to the flight, Tim despairs. He loses his mind in the pain and beats up a woman, accidentally killing her. Later he learns that Liz had nearly succumbed to her cancer on the train to meet Tim, and is taken to a hospital where she dies, but not before giving the attending nurse Fanning's name and phone number. Thus he learns the reason for Liz not meeting at Grand Central Station for their trip to Greece. Depressed and about to be arrested for the murder, Tim asks Jonas Lear for a position in his mission. Tim becomes Subject Zero, the only one of the subjects to survive the infection and retain human form. After hearing his story, Alicia becomes friends with Zero and lives with him for several years. He still is committed to his quest to eradicate the remaining humans and to kill Amy.
During this time Michael has recruited Tifty's men to fund and convert his ship. Ten years later he's nearly finished. Peter is now the president. Michael tries to convince him to allow 600 people to sail to the safe zone, but he fails. After years of conflict, Peter is determined to fight this one to the death. He needs his army. He begins plans for one final showdown by working with Alicia to heal Amy. She is still infected, but she's in human form now. As virals start flanking Kerrvile, Peter's army sets up defenses there. Since the virals can invade from underground, they come out of the battle superior, leaving on 700 refugees left alive by daylight. In light of this defeat, Peter agrees to move everyone onto Michael's ship for a retreat.
Amy and Alicia, with Carter's help, hold off the virals so the humans can escape safely in hopes of establishing a human colony in the Atlantic. Peter and Michael actually stay to try and assassinate Zero. Peter is bitten, but he fights his urges to kill Amy. Instead he attacks Zero, engaging him until the sun rises to do its own damage. Weakened by the sunlight, Zero is easily defeated by Amy at this point. Meanwhile everyone presumes Alicia to have drowned earlier in the fight. Amy gives Peter some of her own blood to save him from the infection. Although Alicia had survived, she awakens free of the virus and decides to kill herself peacefully. At her death, Michael sails to England in hopes of helping those people. Amy and Peter live happily together until he dies of old age and she's alone.
1,000 years later, the survivors aboard the ship have populated an island in the Atlantic. They flourish and spread to repopulate the globe, telling stories of the heroic tales of Peter and Amy. After a millennium they are willing to risk returning to land since the infection will have run its course. Back on the continent of North America, a distant descendent of Peter meets Amy who is still living there in solitude. She tells him the whole story and loves him like a son.
