Twelve-year-old Kester Jaynes has been locked in Spectrum Hall — a home for troubled children — for six years. He has not spoken since his mother died, shortly before he was sent to Spectrum. Kester does not believe his father abandoned him, but he has not heard from his father since being sent away. Hidden behind clouded glass windows, Kester has no idea what is going on in the world outside, only that the government and a giant conglomerate named Facto, which produces food from a place called the Factorium, are trying to keep people alive while a plague devastates all wildlife and crops.
Other children in the home pick on Kester because he does not speak. He finds solace in pretending to talk to the various vermin — bugs and birds that have survived the plague. In his mind, he practices the words he used to say and holds conversations with them. One night he is surprised to learn that the vermin have heard every word and now think he is the one who can save them from the red-eye plague that threatens to kill them all.
Kester follows an army of cockroaches out of Spectrum Hall and is then carried by a flock of pigeons to the only piece of wilderness he has ever seen. The animals there, led by an old but powerful stag, insist that Kester is the one who can find a cure for the plague. Kester knows the only one who could solve the problem would be his father, a veterinarian, but it means going back to the city, which could lead to them getting caught by cullers. Cullers are men sent to kill animals to prevent the plague spreading to humans.
Kester climbs on the old stag’s back and sets off with General, his cockroach friend from Spectrum Hall, who is in his pocket. A flock of pigeons also travels with them and helps scope out a path to the city. A wolf pack tries to stop them from leaving the wilderness, but the stag fights off the pack leader. Later, the wolf’s son joins them to help search for Kester’s father.
When the pigeons give Kester some berries to ease his hunger, he gets sick. Fearful that he has developed the plague, the animals bring him to what they believe to be an abandoned farm. As Kester grows sicker, General helps him to break into the house. They find a girl, Polly, who insists that Kester has come to kidnap either her or her cat, Sidney.
Using Scrabble tiles, Kester explains his mission. Once Polly realizes he is sick, she sets about examining him. She realizes the berries he ate made him unwell. She gives him a concoction of charcoal and flax seed to make him feel better. Polly convinces Kester that Facto has been lying to everyone about the virus when they claim humans can get it from animals. Sidney has been ill for two weeks, and Polly has yet to catch the disease.
Polly explains that her parents refused to leave their farm when the government forced people into the cities. They have been living on what they had in their larder for years, but now their food has run out. Her parents went into the city to try and get some of the formula made by Facto. They said they would only be gone a day, but it has been over a week since they left.
Since they left, Polly has been eating what remains of Sidney’s cat biscuits to survive. Polly insists on traveling with Kester and the animals into the city in the hope she can find her parents, as well as a cure for her cat. As they start to leave the house, they hear a car. Polly hopes her parents have returned, but instead, they meet Captain Skuldiss.
Captain Skuldiss is a tall man who needs metal crutches to walk. He looks for animals that have survived the plague in order to exterminate them. His crutches are equipped with tools such as umbrellas and guns that he can easily retrieve. He travels with several cullers, who begin to search the area for animals to kill.
He forces the children and Sidney into his van to take them to the city. He informs Polly that her parents have been arrested for trying to get Facto formula illegally. He also knows who Kester is and that he is related to the famous veterinarian Professor Jaynes.
The animals rescue the children, and after much arguing, agree to bring Polly and Sidney with them on their mission. Captain Skuldiss and the cullers chase them on foot. Kester and the others must jump into a frigid river in order to escape. Polly and Sidney are dragged toward rapids, but Kester uses his abilities to call snakes to help them. The snakes pull Polly to shore, but Sidney is lost to the water.
Polly has a sprained ankle from her trauma. Kester must search the area for willow leaves that will help Polly’s swollen ankle. While he is gone, people defying the government and living in the country capture her, the stag and General.
Kester sees his friends being carried away on a tractor. He calls to the animals for help. A mouse chews through one of the machine’s wires to stop it. At first, the woman inside claims to want to help Kester and his friends, but he soon learns she and her followers want to eat the animals.
She believes Kester’s father developed the red-eye plague. She leads the stag toward a bonfire, and then gives Kester a knife to kill it. Polly throws a ball of pine resin into the bonfire. It explodes, giving Kester the opportunity to free the stag and the other animals.
The pigeons lead Kester into a dark forest. The other animals grow fearful when they discover it is the place animals go to die. Kester continues further into the woods, while using his telepathic gift to call to any animals still living within the trees.
By the time he leaves the forest, he has added several rabbits, skunks, otters, insects and birds to his motley crew of followers. Kester has also heard the voice of something unseen within the forest. This unseen voice swears it will never follow him but will be his enemy in the future. Sadly, Kester must leave the old stag behind, as the animal is in the last stages of the red-eye plague.
Kester, Polly and their animal crew make their way into the city at night. Kester finds his old house, but when he presses the doorbell, Captain Skuldiss answers the door instead of his father. Skuldiss incapacitates Kester with an electrical blast from his crutch. While Kester is helpless, Skuldiss calls in the cullers to kill the animals.
As he uses his crutch-gun to shoot the animals, one by one, Skuldiss taunts Kester and Polly. A pigeon gives Kester a piece of the old stag’s antler to use as a knife. As he runs toward Skuldiss, so does the wolf cub. The cub is shot just before Kester tackles Skuldiss. The brutal man forces the antler from Kester’s hand. Before Skuldiss can kill more of the animals, the old stag races down the street, using his antlers to scatter the cullers and attacks Skuldiss.
Kester and Polly carry the wolf cub into the house and are thrilled to find Kester’s father inside. Professor Dawson Jaynes has been kept a prisoner in the basement of the house for years. He has been trying to communicate with Kester through the wristwatch the boy wears, but Kester had never understood the random words that popped up on the screen.
Contrary to what they had been told, the professor had not created the virus that caused the red-eye plague, but rather, he had discovered a cure. He went to Facto, hoping they would help him fund the cure, but instead, they locked Kester away at Spectrum Hall and threatened to hurt Kester if the professor tried to make his cure. Instead of helping the animals, Facto wanted them dead so they could make the people dependent on their formula for food.
Unfortunately, Facto destroyed all his research regarding the cure. Kester yells his first word in years: “No!” By repeating the word, he convinces his father to try to recreate the cure. The professor has one sample vile left that they immediately give to the stag. Over the course of the next week, Polly helps the professor collect the plants he needs to make more medicine.
Slowly the injured animals and those who are sick begin to recover, and the wolf cub regains his strength from his wound. Polly and Kester give the pigeons the antidote to take back to the other animals in the wild so they, too, can be healed. At some point, unseen to them, someone comes and removes the bodies of the cullers and Captain Skuldiss from the front yard.
Kester discovers his father can also talk to animals telepathically. As the professor speaks with the stag, Kester learns that he has fulfilled a prophetic dream of the animals. But the stag warns there is more that must happen. Before he can explain further, Kester hears the sound of helicopters arriving.