After the events of the season six finale, Walter Skinner (Mitch Pileggi) and Michael Kritschgau (John Finn) are desperately attempting to find the truth behind the so-called alien object. Meanwhile, Fox Mulder (David Duchovny) is still imprisoned by his own frenetic brain activity. Dana Scully (Gillian Anderson) and Skinner are unaware of FBI Special Agent Diana Fowley's (Mimi Rogers) duplicity—she is working for Cigarette Smoking Man (William B. Davis). Scully then travels to Africa to unravel the secrets of the alien artifacts, finding something that looks like a spaceship buried under the shoreline off the Côte d'Ivoire coast. The object may prove that life originated elsewhere, and all religion is based on the Navajo contact with alien life.  Unsuccessful, Scully returns from Africa to revisit Mulder in Washington, D.C., but instead she finds out that he has disappeared. She contacts Kritschgau and Skinner to find her partner. Cigarette Smoking Man has taken Mulder to a place where all his problems seem to have disappeared. Fowley helps Scully locate Mulder, which leads to her death at the hands of Cigarette Smoking Man. 
While investigating a bizarre disappearance of a young girl from her home, Mulder becomes obsessed with the number of children who have vanished in similar circumstances. Scully fears that he is emotionally involved due to his sister's disappearance.  At the same time it is revealed to him that his mother, Teena Mulder (Rebecca Toolan), committed suicide. He then tries to prove that his mother did not take her own life, but is ultimately forced to accept that his mother's death was by her own hand. He is led by a man whose son disappeared years earlier to another truth—that his sister may be among the souls taken by "walk-ins", saving the souls of children doomed to live unhappy lives. Together they locate evidence that proves that Samantha was abducted by Cigarette Smoking Man and was forced to live in a now-abandoned US Army base. It is later revealed that Samantha had become a "walk-in" spirit. 
Mulder and Scully investigate a case which leads them back to Oregon, the site of their first case together. With a series of Alien abductions taking place, Mulder and Scully are contacted by Billy Miles (Zachary Ansley). Scully falls ill during the investigation and returns to Washington, D.C. Cigarette Smoking Man contacts Marita Covarrubias (Laurie Holden) and Alex Krycek (Nicholas Lea), in an attempt to revive the government conspiracy. With Covarrubias unwilling to assist, and Krycek seeking revenge, they contact Mulder after he visits an alien crash site. Skinner and Mulder return to Oregon, while Scully is hospitalized in Washington, D.C. Mulder becomes trapped by an alien device, and is abducted by an Alien Bounty Hunter (Brian Thompson) together with Miles and several others. Skinner returns to Washington, D.C. where Scully informs him that she is pregnant, though she does not tell him that Mulder is the father.