|My Struggle II||Credits||Gallery|
The investigations that Mulder and Scully previously began with conspiracy theorist and web-TV show host Tad O’Malley (guest star Joel McHale) seem to have awakened powerful enemies. A widespread panic begins as people all over the country suddenly start falling gravely ill, and Scully must look within to try and find a cure. Meanwhile, Mulder confronts the man whom he believes to be behind it all, but another figure from Mulder and Scully’s past shows up.
Six weeks after the events of "My Struggle" Scully arrives at FBI headquarters to find that Mulder has disappeared after watching an excerpt from Tad O'Malley's online news broadcast (which had been revived after being shut down prior). As Scully informs Skinner and Einstein of Mulder's absence, Mulder attempts to leave Washington—visibly unwell, and badly bruised.
Back in Washington, D.C., Scully receives a phone-call from O'Malley, who has arrived at Mulder's house for a pre-arranged meeting to discover that there are signs of a struggle. O'Malley explains that he suspects alien DNA has been injected into every American citizen in order to facilitate the widespread outbreak of a contagion, the Spartan Virus. Designed to strip humans of their immune systems, this contagion quickly begins to manifest itself nationwide, with Scully and Einstein noting a sharp increase in patients admitted to hospitals and triage centers.
Miller, finding a phone-tracking app on Mulder's computer, notes his position at Spartanburg, South Carolina, and leaves Washington in order to track him down, while Einstein questions Scully's medical theories. Scully, accepting that Einstein's doubts may be correct, receives a phone-call from former X-Files agent Monica Reyes (Annabeth Gish), who asks to meet, claiming to know how to develop a vaccine.
During their meeting, Reyes reveals that, shortly after the closure of the X-Files, she was contacted by the badly injured Cigarette Smoking Man, who had survived the confrontation in New Mexico. Cigarette Smoking Man offers to secure both Scully and Reyes a place among the designated survivors of end-times, in exchange for Reyes' assistance in the colonization effort. Reyes departs the FBI shortly thereafter, and is absent when Scully "looks her up" in 2015. Reyes also reveals that she has spent the last twelve years assisting Cigarette Smoking Man, but with the intent to halt the invasion from within the Syndicate.
Scully and Einstein attempt to develop a vaccine using Scully's DNA, as Scully realizes that it is a combination of the alien genomes that remained after she was abducted and tested on, and the DNA anomalies instilled within her at the request of Reyes, that are protecting her from the contagion. It is the absence of alien DNA that is making everybody else susceptible. Mulder, meanwhile, approaches Cigarette Smoking Man, who offers him a chance to survive the outbreak. He declines, and is found by Miller, who returns him to Washington with the hope of finding a cure.
O'Malley tells the nation that his friend, a doctor, has informed him of the existence of a vaccine.
Scully, administering a vaccine to Einstein, travels to Mulder and Miller's location. After finding them at the 14th Street Bridge, she discovers that Mulder is too badly ill to survive without a stem cell transplant. Miller inquires as to how this will be possible, Scully states that it is William, their son, who will have to donate. As Scully and Miller discuss Mulder's prognosis, Mulder begins to succumb to the virus he has contracted. Suddenly, a beam of light shines down onto Miller, Scully, and Mulder, and a triangle-shaped UFO slowly descends and hovers above them.
The episode ends with Scully looking at the lights of the spacecraft, shining down directly onto her and her partners.
- This episode marks the first appearance of Annabeth Gish as Monica Reyes since "The Truth".
- Since Robert Patrick declined to return, the writers chose not to mention his character John Doggett in the episode. Chris Carter explained "We couldn’t use Robert, so we didn’t want to hearken to a character [who was not there]…we wanted to be mindful of all viewers. Her story actually diverged from his, many years ago, so it wasn’t [needed]." 
- This is the first episode to feature Annabeth Gish as Monica Reyes without Robert Patrick as John Doggett.
- Just like the previous season finale "The Truth", Fox Mulder, Dana Scully and the Cigarette Smoking Man are the only characters in this episode to have appeared back in the first episode "Pilot".
- David Duchovny as Special Agent Fox Mulder
- Gillian Anderson as Special Agent Dana Scully
- Mitch Pileggi as Assistant Director Walter Skinner
- Joel McHale as Tad O'Malley
- Lauren Ambrose as Agent Einstein
- Robbie Amell as Agent Miller
- Julian D. Christopher as Dr. Oscar Griffiths
- Annabeth Gish as Monica Reyes
- William B. Davis as Cigarette Smoking Man
- Aliza Vellani as Nurse Sandeep
- Sandy Da Costa as Morphing Alien
- Mik Byskov as Accosting Man
- Darren Dolynski as Man in Suit
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