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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.