With his mother on a deathbed and the alien bounty hunter in pursuit, Mulder decides to put Jeremiah Smith, the alien healer, in mortal danger for a chance to finally uncover the whole truth behind the alien conspiracy. Meanwhile, the Syndicate suspects that they have a traitor in their midst and set up a trap.

The Lone Gunmen reveal the (possibly fake) secret history of the Cigarette Smoking Man to Mulder and Scully; from a young captain in the U.S. Army recruited to assassinate President Kennedy, to becoming the mysterious man in the shadows at the height of a global conspiracy.

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.

Scully's recent failing health is revealed to be an inoperable cancer in her skull, which appears to be common among abductees and she attempts to come to terms with her condition. Meanwhile, Mulder and the Lone Gunmen break into a high-security research lab to find the cure that could save her life.

While celebrating Scully's 33rd birthday, a strange woman informs Mulder that NICAP member Max Fenig (see Fallen Angel) has recently died in a plane crash. After a visit to the crash site and finding Max's body with radiation burns on it, Mulder suggests that the plane was intercepted by a UFO and is rapidly being covered up by the military.

Mulder is arrested for investigating the plane crash and interfering with a military operation, while Scully is caught in an attempted assassination of Corporal Frish which claims the life of Agent Pendrell. Scully bails Mulder out of prison, and they go to Max Fenig's trailer to find out why he was on the plane. Mulder finds evidence of alien technology and boards a plane with it, but the plane is intercepted mid-flight and it disappears. Mulder is again left with nothing.

After a swarm of bees mysteriously kill a postal worker in an enclosed restroom, Assistant Director Skinner covers it up by destroying the evidence. In order to complete the task he poses as Agent Mulder, however his deception backfires. When Mulder finds out and confronts him, Skinner reveals that he is working for the Cigarette-Smoking Man in order to obtain a possible cure for Scully's cancer.

Covered in blood and suffering from amnesia, Mulder pieces together the events of the last few days, but the trail leads to a double murder that appears to have been committed with Mulder's weapon.

Mulder fights to prove that a discovery frozen in the mountains of Canada is an irrefutable evidence of alien life, but his quest for the truth only leads to more lies and an unthinkable conclusion.