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.

While the Cigarette-Smoking Man recites to an unseen listener everything about the work of the Syndicate involving a global conspiracy in cooperation with an alien species, Cassandra Spender reappears and is pursued by the scientists who would rather kill her than keep her alive. Cassandra runs to Mulder's apartment and demands that he shoot her because she is the culmination of 50 years work - a living alien/human hybrid - and colonization will begin if the aliens find out about her.

The Cigarette-Smoking Man reveals all the government secrets from the past 50 years in order for his son, Jeffery Spender, to join him in his work. Mulder learns that the final stage of the conspiracy will soon begin with the hybridization of the Syndicate members, and he must stop it from happening. Agent Spender deceives his father and arranges for Mulder and Scully to be reassigned to the X-Files, which doesn't sit too well with the Cigarette-Smoking Man.