Mulder is less than thrilled when an Office of Professional Conduct board refuses to reassign him and Scully to The X-Files and even more so when he learns that Agent Spender and Agent Fowley have become their successors. When Gibson Praise reappears and comes to them for help, Mulder and Scully attempt to continue their quest undercover despite having fewer friends and less access and protection than ever before.

Mulder is trapped in a car with a man who has developed a serious ear condition which can only be suppressed by driving west at high speeds. As Scully tries to find the cause and a cure for the problem, Mulder and the man get closer and closer to the ocean.

While being detained near the famed "Dreamland" Area 51, a strange craft flies overhead and Mulder swaps bodies with an Area 51 "Man-in-Black". While the other agent has fun in Mulder's body, Mulder himself finds it difficult to fit into someone else's life, especially a shadowy one. Mulder contacts Scully about the body swap and tries to get her the flight data recorder from the UFO test flight, but his alter ego uses Mulder's FBI persona to have him arrested.

Assistant Director Kersh tries to tear Scully and Mulder apart when he partners Scully with a New York agent investigating Alfred Fellig, a freelance police photographer who conveniently shows up to document the scene of a death as soon as it happens.

While the young hotshot agent is convinced that Fellig is murdering the people, Scully has other (paranormal) theories.

The Cigarette-Smoking Man reveals all the government secrets from the past 50 years in order for his son, Jeffery Spender, to join him in his work. Mulder learns that the final stage of the conspiracy will soon begin with the hybridization of the Syndicate members, and he must stop it from happening. Agent Spender deceives his father and arranges for Mulder and Scully to be reassigned to the X-Files, which doesn't sit too well with the Cigarette-Smoking Man.

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.

Working without Scully's input, Doggett and Skinner try to stop the mysterious murder spree of a drug-induced religious cult leader, and it becomes clear that the man can enter the dreams of the people he knows and can kill them in their sleep.

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, 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.

Agent Doggett investigates the death of an EPA official after his car is forced off a bridge by a woman he picked up. He asks for assistance on the case from Scully, who has returned to her teaching position at the FBI Academy in Quantico.

Doggett catches up with Shannon McMahon, the woman who the EPA official picked up. She claims to be a super solider and that the people she has killed were poisoning the water supply, and she wants Doggett to expose the truth.

Scully and Reyes join forces to try and find Doggett when he goes missing. Doggett has his own problems, having woken up in jail in Mexico suffering from amnesia. With no knowledge of who he is, Doggett is befriended by a local who soon has him working smuggling illegal immigrants across the border.

When pieces of the spaceship beached in Africa resurface, the conspiracy within the FBI attempts to hide the information from the X-Files, especially the one person for whom the pieces have a special significance - Scully. When Doggett and Reyes discover that Scully and her child have been put in great danger, they race to protect her and William from the evil forces pursuing him, and Scully is forced to take drastic measures to protect her child.

Scully is anxious to recover William from his kidnappers and takes matters into her own hands when the FBI's attempts to assist in the investigation are less than helpful. With the help of the Lone Gunmen, Scully discovers terrifying information about her child's captors, and is once again forced to confront the mystery regarding the sinister interest in her son.

After not knowing Fox Mulder's whereabouts for the last year, A.D. Skinner and Agent Scully learn he's being held for the murder of a military man he couldn't possibly have killed: Knowle Rohrer, one of the government's secret super-soldiers. With Skinner acting as Mulder's defense, people who Mulder has dealt with during his last nine years as an FBI agent testify on his behalf. But the military tribunal isn't interested in the truth.

Skinner goes AWOL when his past comes back to haunt him. As Mulder and Scully try to track him down, their growing mistrust of him reaches its apex.

Mulder and Scully rush to find an on-the-run William while the Cigarette Smoking Man pushes forward with his ultimate plan.