The X-Files has been shut down and Mulder and Scully are separated. Scully finds herself teaching classes at the FBI Academy in Quantico, Virginia, while Mulder is assigned to surveillance duty. With Agent Alex Krycek as his new partner, and the mysterious X as his new source of information, Mulder struggles to keep his search for the truth alive. But ironically it is Scully who experiences the close encounter Mulder has longed for, taking a journey that will ultimately bring the two agents back together and forging a bond that will make them closer than ever before.
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.
A.D. Skinner sends Mulder to investigate a body which washed into the New Jersey sewer from the ocean. Mulder believes that the basic blue-collar assignment is punishment, but by Skinner's own admission, what he discovers is a true X-File.
When several violent deaths in a small farming community are connected by the destruction of digital devices, Mulder believes that people are being driven to kill by the use of subliminal messages in the digital readouts.
Mulder reluctantly accepts a new partner, Agent Alex Krycek, and they investigate the deaths of several Green Beret soldiers who participated in a sleep deprivation experiment during the Vietnam war.
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.
Mulder, back on the X-Files but alone for the first time, investigates a series of vampire-like murders in Los Angeles and finds himself falling for the one woman that may be the prime suspect.
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.
Mulder and Scully, reunited at last, head for an active volcano under a geological study and find a deadly life form that can survive in the searing heat of the crater and is killing the scientists to avoid being discovered.
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.
Mulder and Scully uncover strange occurrences in an elderly care home when one of the nurses is attacked by an unseen force she claims to be one of the 90 year old residents.
When a detective mysteriously uncovers the remains of an FBI agent who disappeared in the 1940s while investigating a similar murder case to one she is now on, Mulder and Scully believe that the original killer had passed his genetic trait of violence to his grandchild.
A mortuary worker who gets his thrills from collecting hair and fingernails from the dead begins killing his soon-to-be collectibles himself and sets his seriously disturbed sights on Scully.
The ritualistic murder of a teenager in a small town gets Mulder and Scully caught up in a secret occult practice within the local school's PTA and a substitute teacher with strange powers.
While investigating several deaths and murders within a Haitian refugee camp, Mulder and Scully get caught in the middle of a secret war between the camp commander and a Voodoo priest.
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 and Scully investigate strange attacks from invisible animals inside a zoo which is near a known UFO hot spot.
When half the crew of a Navy ship abandon their boat in a life raft and are rescued 18 hours later looking about 60 years older than they should be, Mulder suggests that the ship is caught in a time field which is speeding up their aging.
Mulder and Scully travel to Gibsonton, Florida, a town built and populated by circus and sideshow performers to investigate the death of Jerald Glazebrook, The Alligator Man. While searching for leads on the killer, the agents come across many bizarre characters including the local sheriff who was once known as Jim Jim, the Dog-Faced Boy.
The suspicious circumstances of a toddler's death leads Mulder and Scully into a Romanian exorcism ritual involving a young boy possessed by his stillborn twin.
When a plague-like illness kills ten men inside a maximum security prison, Scully tries to get into the quarantine site and discover the cause and origin of the contagion, while Mulder and a group of US Marshals track two escapees who may be infected.
An experiment in dark matter accidentally turns a scientist's shadow into a deadly weapon that can unzip a person's molecules if they are touched by it.
After several disappearances in a small town, Mulder and Scully investigate and find hundreds of human bones in the river. They discover that the man behind the town's main source of wealth, a chicken processing plant, has found a way to prolong his life through cannibalism.
When Mulder obtains what could be the original and uncut MJ documents containing information about the government's knowledge of extraterrestrial life; his shadowy enemies step up their harassment of him, eventually leading to his apparent murder.