The agents' first case takes them to Oregon to investigate the unsolved murders of several high-school classmates.

As Section Chief Blevins expresses his concern with the direction of the X-Files, Mulder becomes obsessed with solving a case that closely parallels an encounter he experienced as a child: the abduction of his kid sister, Samantha.

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.

Scully helps Mulder fake his own death in order for him to go undetected through the Department of Defence and find out the answers to his new questions about the government hoax concerning the existence of extraterrestrial life. Meanwhile, at a joint FBI/DOD inquiry, Scully's attempt to drive out the Conspiracy's informant is halted as her cancer takes a bad turn.

The Cigarette-Smoking Man helps Mulder to obtain Scully's cure and also lets him see his real sister who doesn't turn out to be as happy to see Mulder as he would've liked. In return for this, the Cigarette-Smoking Man asks that Mulder quit the FBI and work for him in the Syndicate where he could have power and respect which Mulder turns down, deciding to stay on the side of justice. While Scully's cure appears to have worked, the Cigarette-Smoking Man faces his own enemies and disappears, presumed dead.