Scully finds her career with the FBI in jeopardy as Mulder is still missing and the Cigarette Smoking Man is pursuing the stolen files. The Navajo elders find Mulder's body in a cave and perform an ancient ceremony to call the spirit back to the empty vessel.

A.D. Skinner and Scully are at a standoff when Mulder bursts in and discovers that Skinner has the digital tape. Reunited, Mulder and Scully travel to a secret vault inside a mine and find an elaborate filing system of medical records which reveals that Mulder's sister may not have been the first choice for abduction. Meanwhile, Skinner deals with the Cigarette-Smoking Man for their safety.

Mulder pursues Krycek (unaware of the alien that has taken over his body) to get back the DAT tape containing the MJ documents. Meanwhile, the shooting of A.D. Skinner uncovers evidence that could lead Scully to her sister's murderer.

Mulder is given a tip about potentially dangerous paramilitary operations on the U.S. soil but during the sting operation is surprised to find out the identity of his mysterious informant - it turns out to be Alex Krycek. Suspicious about his true motives, Mulder reluctantly follows the information provided by Krycek. However, soon he discovers a much bigger conspiracy which takes him to a gulag in Tunguska, Russia where prisoners are being used for experiments involving a substance of alien origin.

While imprisoned in Russia and infected with the Black Cancer, Mulder learns that Krycek is working with the men responsible and everything has been a setup from the start, while Scully and Skinner are called to a suspicious Senate hearing where the only question is the whereabouts of Agent Mulder.

Mulder and Scully meet Cassandra Spender, a woman who claims to be a multiple abductee and wants to deliver a positive message about the aliens. Mulder's new found disbelief in extraterrestrial activity is enhanced while Scully forms a special bond with the woman. A series of group attacks against abductees take place and the shadowy Syndicate believes that a rebel alien resistance is attempting to destroy all their work.

After the gathering at the abduction site where everyone is killed by the rebel bounty hunters, Cassandra Spender disappears and Mulder is blamed by her son, Jeffrey, who is an up-and-coming FBI agent. Meanwhile, the Syndicate is continuing their tests to create a vaccine for the Black Cancer and Marita Covarrubias becomes an unwilling test subject.

The Cigarette-Smoking Man returns as Mulder investigates the attempted assassination of a young boy with psychic powers who may be the proof that he has looked for all his life.