When the ship docks, an irate Dr. Ian Detweiler, the owner of the container, sees that a pool of blood has oozed out of the crate and is furious that the animal contained within may have been hurt. When they remove the outer locks and open it, however, it is the two crew members who lie dead at the bottom of the crate; the animal nowhere to be found.

Mulder is tipped off to the event and after some preliminary investigating, finds that the ship's manifest listed the animal as a dog. When he theorizes that a dog might have been responsible for the deaths of the two crewmen, Scully reminds Mulder that in order for that to have happened, the dog would've had to escape from the box, kill the two men, put them back inside and lock the crate behind them -- hardly the actions of man's best friend.

On board the T'ien Kou, Fish & Wildlife Department officer Jeffrey Cahn takes Mulder and Scully to meet Detweiler, who tells them that the dog is a Wanshang Dhole, a very rare breed of canid from Asia thought to be extinct for the past 150 years. Just as Detweiler is explaining that the dog does not have a predatory nature, a US F& W officer reports that another dog attack has occurred.

Mulder and Scully pay a visit to Karen Berquist, the canine behavioralist who gave Mulder the tip about the first murders - she and Mulder had been communicating via the Internet. They hope Berquist might be able to shed some light onto the behavior of the animal. As they wait in her library, Scully notes a copy of the "I WANT TO BELIEVE" poster hanging on Berquist's wall. When Berquist finally arrives, she is less than hospitable. She tells the agents that while some canids use tricks to draw out their prey, they do not possess the intelligence to murder; murder is a human behaviorism. While Mulder believes Berquist, Scully is suspicious of her motives, thinking that Berquist may have tipped off Mulder so that she could meet him.

The assaults continue. A U.S. Fish & Wildlife officer and a veterinarian are attacked and killed. Detweiler maintains that the dog can be captured, but Cahn is incensed and wants the animal killed. Then Cahn himself is attacked but somehow manages to escape death and is rushed to the hospital.

Mulder finds Detweiler in Cahn's hospital room and confronts him with the theory that it is Detweiler who is responsible for the murders. Mulder posits that while Detweiler was in Asia hunting the Dhole, the Dhole found and attacked him, turning him into a shapeshifting trickster who can take the form of an animal. Detweiler denies Mulder's outrageous theory and leaves. Mulder then repeats his ideas to Berquist who confirms them. She tells Mulder to stay at the hospital and guard Cahn; Detweiler will want to come back and put down the threat he failed to eliminate by attacking Cahn.

Hours pass, but Detweiler never returns. Mulder realizes that Berquist lied to him. Detweiler, feeling a much larger threat from Berquist, has gone to Berquist's home to kill her. Once there, he takes the shape of the wild dog and attacks. Berquist stands her ground, and as the dog leaps, Berquist falls backward through the second-story window. When Mulder and Scully arrive, they find both Berquist and Detweiler dead.

Yet Berquist leaves somewhat of a legacy to Mulder. Upon his return to Washington, he receives a package in the mail - her copy of the symbolic "I WANT TO BELIEVE" poster that Mulder had lost in the fire in "The End" (Episode 5X20).