At the Teso Dos Bichos excavation site in South America, Secona Indian diggers uncover an Amaru urn embedded in the wall of a burial mound. The urn contains the remains of a female shaman, which the Indians believe is sacred to their tribe. Bilac, a Brazilian-born man acting as dig coordinator, tells Dr. Roosevelt, the American leader of the expedition, that the urn should be left undisturbed. But Roosevelt insists it be transported back to the United States. Later, Bilac participates in an Indian tribal ceremony and consumes a strange liquid called yaje. Moments later, a jaguar-like form attacks Roosevelt inside his tent, killing him.

At the Museum of Natural History in Boston, a night watchman discovers the body of Mr. Horning, who participated in the archeological project. Dr. Lewton, the museum's coordinator, suspects that the murder may be an act of political terrorism. Mulder tells Scully that the Secona Indians believe great evil will befall anyone who disturbs the remains of an Amaru, a woman-shaman.

The agents question Bilac, who admits he objected to the dig from the very beginning. Scully believes it was Bilac who murdered Horning, and not a mythological Jaguar spirit sent by the Seconas. Later, Dr. Lewton is attacked by an unseen force as he works under the hood of his stalled Jaguar automobile.

The agents search the area around the museum hoping for clues. Scully finds body parts of dead rats wedged inside the engine. She suspects the animals were attracted by the car engine's warmth. While searching nearby woods, Mulder discovers Lewton's eviscerated remains dangling from a tree.

Mona Wustner, a grad student researcher, phones the agents with news that Bilac made frightening comments to her. Inside the woman's washroom at the museum, Mona discovers rats trapped within a toilet. But when Mulder arrives at the museum, Mona has disappeared.

Scully, meanwhile, gains access to Bilac's residence. She finds the liquid yaje inside a ceremonial bowl, and reads journal entries indicating that Bilac has invoked the Amaru curse.

Mulder discovers Bilac inside the woman's washroom at the museum. He claims Mona is dead, but insists he does not know where to find the body. Bilac is placed in a room guarded by security men.

The agents find the dead body of Mona's dog, Sugar. A veterinarian performs an autopsy and discovers evidence that the dog had eaten a cat which had devoured a poisoned rat. Mulder concludes the rats are trying to get away from something.

Bilac disappears. The agents suspect he escaped into steam tunnels that run beneath the museum. Pulling up a manhole cover, the agents descend into the darkness. They discover Dr. Lewton's partially-devoured body parts... and dozens of ravenous house cats. Mulder rescues Scully after she is attacked by a cat. But the felines give chase, and the agents take refuge inside a room. As a sea of cats mass for another attack, the agents discover Bilac's body stuck inside an air vent. Realizing the vent is their only means of escape, Mulder and Scully dislodge the body and make their way to safety. Animal control is dispatched to hunt down the rampaging felines, but cannot locate them in the miles of steam tunnels. Mulder receives word that the State Department is returning the urn to Ecuador.