Newly appointed Deputy Director Kersh organizes a manhunt for Mulder and assigns Agent John Doggett to head the team. Scully and Skinner go along with the investigation but are warned by Kersh that they will be fired if anything is said about aliens. Scully, along with the Lone Gunmen, surmise that the Bounty Hunter is trying to erase all evidence of abductions, and they realize that he may be going after Gibson Praise, who is now living at a school in Arizona. Agent Doggett comes to the same conclusion and his team race Scully and Skinner to the school where they find Mulder trying to kidnap Gibson.

As the search for Mulder intensifies in the Arizona desert, Gibson Praise leads Scully to believe that she is truly closer to her target. Meanwhile, A.D. Kersh informs Agent Doggett that he has been assigned as Mulder's successor on the X-Files.

Doggett comes upon an old case that Mulder kept secret from Scully and he follows up the investigation, hoping to find a possible connection to Mulder's disappearance.

When Scully and Doggett are contacted by a man who claims his wife was murdered shortly after giving birth to an alien baby, Scully digs deeper into reports of alien fertilization on humans, and she begins to question her own pregnancy and its conception.

When Teresa Hoese (the woman Scully and Mulder met the previous spring in Oregon just before Mulder was abducted) is found in a desert after enduring alien testing, Doggett alerts Scully that this could have something to do with Mulder and his whereabouts. Skinner joins them and they travel to the hospital where Teresa is clinging to life by a thread, and Scully realizes that this is exactly what's going on with Mulder.

Shortly after Mulder is buried, Billy Miles is found very dead, but he somehow comes back to life. Skinner and Scully put all their hopes into digging up Mulder and discovering that he too, is still alive. As Mulder lies in the hospital without indication that he is going to fully recover, Krycek comes to Skinner and offers him a vaccine to the virus that has infected Mulder, but the cost of the vaccine is that Skinner has to kill Scully's unborn child.

Mulder's request for reassignment to the X-Files is denied by Kersh, who hopes that Mulder will simply quit the FBI. When a census worker is killed on the White House lawn trying to get information to the President, Mulder gets in over his head trying to discover what the man knew.

Mulder and Doggett are reluctantly thrown together to investigate several deaths aboard an oil rig, and Mulder becomes convinced that the rig is really carrying the black oil alien.

Mulder and Doggett join forces to investigate the arson attack on a genetics lab where one of the doctors suspected of experimenting with alien impregnation is killed. They encounter Billy Miles, who has been changed into an alien replicant after his recent abduction and is attempting to erase evidence of the tests. When a woman helping Scully out at home is found to be a part of the conspiracy, the agents, along with Monica Reyes and Alex Krycek, know they must protect Scully and her baby from Billy Miles and get her out of the city.

Mulder, Doggett and Skinner attempt to fight off the alien replicants, and they find a connection to the conspiracy that leads into the FBI while Reyes and Scully head to a remote farm to safeguard the birth of Scully's child.