Dana Scully (Gillian Anderson) is reassigned to teach at the FBI Academy while Fox Mulder (David Duchovny) is given lowly surveillance assignments. After he investigates extraterrestrial cases at the Arecibo Observatory in Puerto Rico,  Mulder is given a new partner, Alex Krycek (Nicholas Lea), and meets a secretive informant, X (Steven Williams).  Mulder is recruited to assist in a hostage negotiation when Duane Barry, an alien abductee, captures four people.  Barry eventually kidnaps Scully, believing that if he brings her to his original abduction site, Skyland Mountain, aliens will take her instead of him. Mulder follows but is delayed by Krycek, who is revealed to be a mole working for Cigarette Smoking Man (William B. Davis). When Mulder reaches Skyland Mountain, Scully is gone. Barry, who insists that aliens took him, dies soon after an interrogation by Krycek. When Krycek vanishes, Skinner re-opens the X-Files, claiming that is what the conspirators will fear most. 
Scully turns up comatose in a hospital four weeks later with no explanation about how she got there. X provides Mulder with information allowing him to take revenge on her captors, but Mulder is instead convinced by Scully's sister Melissa to visit her bedside. Scully recovers and returns to work shortly thereafter.  The agents later investigate a case involving alien biology being injected into teenagers in Wisconsin, and once again they encounter Deep Throat's killer, who is killed by the local sheriff. 
When investigating a case involving the murder of identical doctors, the agents come across a shapeshifting Alien Bounty Hunter (Brian Thompson) responsible for executing a series of alien clones. During this case a grown woman claiming to be Mulder's sister Samantha appears, telling Mulder of the Bounty Hunter's objectives and that she has the ability to identify him.   When Scully is kidnapped by the Bounty Hunter, Mulder is forced to trade Samantha for her. During a botched attempt to kill the Bounty Hunter, Samantha is killed. However, it is discovered that this was simply one of many alien clones of Samantha. With the help of X, Mulder pursues the Bounty Hunter to a submarine in the Arctic. Mulder is nearly killed when exposed to the Bounty Hunter's toxic blood, but is saved by Scully. 
When a hacker downloads decades' worth of classified information about aliens onto a digital tape, he gives it to Mulder, who finds that the entire tape is written in Navajo. Cigarette Smoking Man begins searching for the tape and visits Mulder's father, who calls Mulder to see him shortly afterwards. Before he can reveal anything to Mulder, however, he is murdered by Alex Krycek. Scully brings Mulder to New Mexico, where she introduces him to Albert Hosteen, a code-talker who can translate the digital tape. Albert's grandson shows Mulder a boxcar filled with alien corpses. Cigarette Smoking Man tracks Mulder's location, however, and orders the boxcar burned.