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.

After his mother suffers a stroke under strange circumstances, Mulder searches for a strange, benevolent alien man that possesses miraculous healing powers. With the help from Mr. X, he learns about the involvement of the Cigarette-Smoking Man and uncovers some secrets kept by his parents.

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.

Mulder and Scully meet Cassandra Spender, a woman who claims to be a multiple abductee and wants to deliver a positive message about the aliens. Mulder's new found disbelief in extraterrestrial activity is enhanced while Scully forms a special bond with the woman. A series of group attacks against abductees take place and the shadowy Syndicate believes that a rebel alien resistance is attempting to destroy all their work.

After the gathering at the abduction site where everyone is killed by the rebel bounty hunters, Cassandra Spender disappears and Mulder is blamed by her son, Jeffrey, who is an up-and-coming FBI agent. Meanwhile, the Syndicate is continuing their tests to create a vaccine for the Black Cancer and Marita Covarrubias becomes an unwilling test subject.

Mulder meets with Agent Arthur Dales' brother (also named Arthur) and is told a tale of a talented negro baseball player from Roswell, New Mexico in the 1940's who may have been an alien that ran away from his colony because of his love for the game.

Mulder and Scully return to the town of their first X-Files investigation where a UFO has crashed in the forest. The Cigarette-Smoking Man arranges for Krycek to be released from prison in order for him to make contact with the aliens and begin rebuilding the "Project", while Scully's health appears to be taking a turn.

As the search for Mulder intensifies in the Arizona desert, Gibson Praise leads Scully to believe that she is truly closer to her target. Meanwhile, A.D. Kersh informs Agent Doggett that he has been assigned as Mulder's successor on the X-Files.