The exploits of FBI Special Agents Fox Mulder and Dana Scully who investigate X-Files: marginalized, unsolved cases involving paranormal phenomena. Mulder believes in the existence of aliens and the paranormal while Scully, a skeptic, is assigned to make scientific analyses of Mulder's discoveries that debunk Mulder's work and thus return him to mainstream cases.
With his mother on a deathbed and the alien bounty hunter in pursuit, Mulder decides to put Jeremiah Smith, the alien healer, in mortal danger for a chance to finally uncover the whole truth behind the alien conspiracy. Meanwhile, the Syndicate suspects that they have a traitor in their midst and set up a trap.
A baby is found buried alive in shallow ground and appears to have birth defects resulting from generations of inbreeding, leading Mulder and Scully to a reclusive family who have a history of inbred children.
After several African-American men are killed and the color is drained from their skin, Mulder learns about the Teliko, an African folktale about a creature who must suck the pigmentation from a persons body in order to survive.
Several kidnappings of young women linked by distorted photographs lead Mulder and Scully to a man who can imprint his darkest fantasies onto undeveloped film and is trying to save the women from the "howlers".
After an FBI raid on a doomsday cult called the "Temple of the Seven Stars", Mulder meets Melissa, a cultist who claims to have known him in a previous life during the American Civil War. Scully believes the woman is a delusional schizophrenic, but Mulder allows himself to be drawn into her fantasies.
After a doctor loses control and kills a patient on the operating table, Scully hypothesizes that it's linked to work-related stress, while Mulder is convinced of a more sinister reason. After he finds a link between the victim and the four witches Sabbaths, he suspects that a nurse may be practicing witchcraft.
The Lone Gunmen reveal the (possibly fake) secret history of the Cigarette Smoking Man to Mulder and Scully; from a young captain in the U.S. Army recruited to assassinate President Kennedy, to becoming the mysterious man in the shadows at the height of a global conspiracy.
Mulder is given a tip about potentially dangerous paramilitary operations on the U.S. soil but during the sting operation is surprised to find out the identity of his mysterious informant - it turns out to be Alex Krycek. Suspicious about his true motives, Mulder reluctantly follows the information provided by Krycek. However, soon he discovers a much bigger conspiracy which takes him to a gulag in Tunguska, Russia where prisoners are being used for experiments involving a substance of alien origin.
While imprisoned in Russia and infected with the Black Cancer, Mulder learns that Krycek is working with the men responsible and everything has been a setup from the start, while Scully and Skinner are called to a suspicious Senate hearing where the only question is the whereabouts of Agent Mulder.
Mulder's dreams help him in finding the body of a little girl which reopens one of his old cases in the Violent Crimes Unit. This leads him to believe that the killer he captured had more victims and that Mulder's sister Samantha may have been one of them.
After a strange yellow rain kills a migrant girl, her family believes that a mythical creature el chupacabra was the cause and that it has manifested itself inside her fiancé's brother, who has since disappeared.
After the body of a decapitated EMT disappears from the morgue and an identical man starts work at the same hospital, Mulder believes that the man has the ability to regrow parts of his body, including his head. The agents soon discover that Betts' body is riddled with cancer and he is able to live in that condition but needs to feed on cancerous tumors to keep up his strength.
While Mulder is forced to take a vacation he leaves Scully with an assignment to keep her busy until he returns. However, she decides to start living and goes on a date with a man who believes that his tattoo talks to him and is telling him to stay away from other women.
Scully's recent failing health is revealed to be an inoperable cancer in her skull, which appears to be common among abductees and she attempts to come to terms with her condition. Meanwhile, Mulder and the Lone Gunmen break into a high-security research lab to find the cure that could save her life.
After a Jewish man is murdered in a Jewish community, his killers are murdered, too. Mulder and Scully have to determine whether someone is exacting vengeance or larger forces are at work.
When a U.S. military general is inexplicably murdered in the back of his limousine, a paramilitary group is suspected. They believe it was a soldier who they liberated from a Vietnam POW camp and is plotting to kill certain corrupt military figures.
While celebrating Scully's 33rd birthday, a strange woman informs Mulder that NICAP member Max Fenig (see Fallen Angel) has recently died in a plane crash. After a visit to the crash site and finding Max's body with radiation burns on it, Mulder suggests that the plane was intercepted by a UFO and is rapidly being covered up by the military.
Mulder is arrested for investigating the plane crash and interfering with a military operation, while Scully is caught in an attempted assassination of Corporal Frish which claims the life of Agent Pendrell. Scully bails Mulder out of prison, and they go to Max Fenig's trailer to find out why he was on the plane. Mulder finds evidence of alien technology and boards a plane with it, but the plane is intercepted mid-flight and it disappears. Mulder is again left with nothing.
A case involving a strange old man warning two scientists of events in the immediate future which come to pass (and the use of their experimental flash-freezing compound that does not exist yet) has Mulder believing that one of the scientists has come from the future to stop his own scientific breakthrough from becoming reality.
Five babies in the same town are all born with tails and the local OB-GYN is blamed for tampering with fertilized eggs. However, Mulder discovers the culprit to be a simple man with a genetic deformity who may have the ability to alter his appearance.
After a swarm of bees mysteriously kill a postal worker in an enclosed restroom, Assistant Director Skinner covers it up by destroying the evidence. In order to complete the task he poses as Agent Mulder, however his deception backfires. When Mulder finds out and confronts him, Skinner reveals that he is working for the Cigarette-Smoking Man in order to obtain a possible cure for Scully's cancer.
After a man sees a woman trapped inside a bowling alley pin setter, he goes for help and finds police standing next to a body of the same woman. Mulder and Scully join the investigation and follow up this lead which the police won't bother with, and they are led to a mentally challenged man who works at the bowling alley.
Covered in blood and suffering from amnesia, Mulder pieces together the events of the last few days, but the trail leads to a double murder that appears to have been committed with Mulder's weapon.
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.
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