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.

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.

When Deep Throat points out a news story about a fugitive who apparently drowned, Mulder and Scully cannot see what makes the case special but follow it up anyway. With Deep Throat’s insistence, they discover evidence of a secret government project code-named Purity Control, which uses human test subjects and infects them with extraterrestrial DNA. However, the evidence and everyone who has seen it is quickly being eliminated.

Mulder and Scully investigate the death of a scientist working on advanced propulsion technology. The mentally challenged janitor Roland, who has secretly been completing the scientist’s work, is the prime suspect.

After a detective and his former partner die in unexplained circumstances, the accidents are linked to a little girl who witnessed both deaths. Mulder believes that she may be the reincarnation of a policeman murdered by his colleagues.

Eugene Tooms is released from the sanitarium, and Mulder becomes personally involved to ensure that he is caught in the act of getting the last human liver he needs to go into hibernation for another 30 years.

When a group of loggers in the Washington State National Forest disappear in the same way that another group disappeared 50 years ago, Mulder and Scully go along to investigate and find themselves trapped in a cabin surrounded by flesh eating insects that only attack at night.

Mulder and Scully travel to a Native American reservation to investigate the death of a man who was mistaken for a wild animal and may have been the legendary Manitou, a man who can shape-shift into a beast.

Agent Dana Scully is assigned to work with Agent Fox Mulder on the X-Files in an attempt to debunk his work on the paranormal. Their first case takes them to Oregon to investigate the unsolved murders of several high-school classmates.

The season concludes with people all across the country falling gravely ill. A widespread panic develops and Scully looks within to find a cure. Meanwhile, Mulder confronts the man he believes to be behind it all, but another figure from Mulder and Scully’s past may prove to be the key to their salvation.