John Shiban's original idea for the script was to have Mulder on the cusp of dying. Frank Spotnitz persuaded him that audiences wouldn't buy that the show was prepared to kill off their lead character, whereas there would be some doubt if they used a secondary character instead.
Mitch Pileggi, who had boxed competitively in college, went for refresher courses at the Goosen Gym in Los Angeles.
The name of Dr. Orgel's character is an homage to the real Leslie Orgel, who was known for his theories on the origins of life and self-replicating molecules such as catalytic RNA.
The doctor and nurse that examine Skinner make jokes about Skinner not losing an ear during his boxing match. This is in reference to when professional boxer Mike Tyson bit off part of opponent, Evander Holyfield's ear during a then-recent fight.
This is the final appearance of Senator Matheson.