Fox Mulder and Dana Scully have been contacted by Tad O’Malley, a popular conspiracy theorist web-TV show host who believes he has uncovered a significant government conspiracy. With the assistance of FBI Asst. Dir. Walter Skinner, O’Malley seeks to enlist the help of former X-Files agents Mulder and Scully, who have since severed ties with the FBI. Through O’Malley they are introduced to Sveta, a possible alien abductee who shares shocking information with them that will challenge everything that Mulder has ever believed about the existence of aliens and the government’s role in covering them up.

A scientist commits suicide, and Mulder and Scully investigate what unseen force may have driven him to it. They uncover a laboratory where extreme genetic experimentation has been going on for decades. The breeding subjects possess unexpected and dangerous powers, and harbor deep resentments.

A dead body is found in the woods. Mulder and Scully try to find out whether it was an animal attack, a serial killer or just a strange creature. Meanwhile, Mulder is able to confront some of his own demons about feeling disillusioned with his life's work.

Mulder and Scully are sent to investigate the murder of a city official, which no human could have committed. Scully deals with a personal tragedy, which brings up old feelings about the child she gave up for adoption.

An art gallery that's showing potentially offensive artwork is bombed, and Mulder and Scully try to communicate with the comatose bomber to prevent a future attack. A pair of younger FBI agents on the case push Mulder and Scully to examine their own beliefs.

The investigations that Mulder and Scully began with Tad O’Malley have awakened powerful enemies. A panic begins as people all over the country suddenly start falling ill, and Scully looks for a cure. Mulder confronts the man whom he believes to be behind it all, but another figure from their past may prove to be the key.