Agents Mulder and Scully return after 13 years to investigate a government conspiracy at the behest of a popular web-TV-show host, who introduces them to a woman who claims she's an alien abductee and shares startling news with them.

When Mulder and Scully try to discover what unseen force may have driven a scientist to commit suicide, they turn up a laboratory where extreme genetic experimentation has bred subjects possessing dangerous powers.

Mulder and Scully investigate a dead body in the woods, and try to determine whether it was the work of a serial killer, an animal or a mysterious creature seen by eyewitnesses. Meanwhile, a disillusioned Mulder confronts some of his own demons.

Scully and Mulder investigate when an art gallery displaying offensive artwork is bombed, and need to discover a way to communicate with the comatose perpetrator to try and prevent a future attack.

The season concludes with people all across the country falling gravely ill. A widespread panic develops and Scully looks within to find a cure. Meanwhile, Mulder confronts the man he believes to be behind it all, but another figure from Mulder and Scully's past may prove to be the key to their salvation.