With the X-Files closed, Scully has been assigned as an instructor at the FBI Academy while Mulder is doing menial surveillance work. After meeting with Senator Matheson, one of his supporters in regards to the X-Files, Mulder disobeys orders and heads to an abandoned SETI site in Puerto Rico which has inexplicably reactivated itself and could provide proof of contact with extra-terrestrial life.

Mulder is called to a hostage situation involving Duane Barry, a former FBI Agent who claims to be an alien abductee and wants to get back to the abduction site with someone who will be taken instead of him. Unfortunately, the someone he eventually chooses is Scully.

When Mulder finds out that Scully was kidnapped by Duane Barry, he risks the wrath of his superiors and the annoyance of Agent Krycek in order to do whatever it takes to find her. Meanwhile, Krycek is found to be reporting Mulder's activities to the Cigarette-Smoking Man.

Scully mysteriously appears in a Washington hospital, alive but in a coma, and Mulder must fight to keep her alive in order to find out what happened to her and who did it to her. Meanwhile, Scully fights her own personal battle as she decides whether to stay or go on to the next world.

While investigating the connection between the abduction of several teenagers and a rural religious cult, Mulder and Scully discover a secret test being performed on the children using the "Purity Control" alien DNA from 'The Erlenmeyer Flask' which leads Mulder to "the crew-cut man", Deep Throat's murderer.

After the obituaries of four identical men are e-mailed to Mulder, the agents are contacted by a shadowy CIA agent who tells them about a bounty hunter sent to wipe out the beginning of a colony of clones. Meanwhile Mulder is distracted by the sudden reappearance of his sister Samantha.

The alien bounty hunter kidnaps Scully and wants to trade her for Mulder's sister, who is revealed to be a clone herself. After the trade goes badly and Mulder discovers the truth about Samantha, he tracks the bounty hunter to his ship buried in the arctic ice and demands the whereabouts of his real sister.

Mulder receives an encrypted computer disk containing the defense department's top secret files on extraterrestrial life and becomes a target. Scully takes him to a Navajo family that unearthed a buried secret to decipher the disk.