This movie is dedicated to Randy Stone, the casting agent who cast Pilot (1993), and who found David Duchovny to play Fox Mulder and Gillian Anderson to play Dana Scully. Stone died in 2007.
Chris Carter originally planned to make this movie right after the end of Los expedientes secretos X (1993), and use it to end the alien invasion story line. Since production was delayed for over five years, Carter decided to focus on a standalone mystery in order to make the movie appealing to people who weren't familiar with the show's mythology, leaving the invasion subplot for a possible third movie.
At the end of the scene where Dana Scully is discussing the options for her patient with the hospital administrators, on the wall behind her are several photographs of priests. The last one is a photograph of Bruce Harwood, who played John Fitzgerald Byers, one of the three Lone Gunmen from Los expedientes secretos X (1993) and its spin-off series, The Lone Gunmen (2001).
Mitch Pileggi stated at a convention that the plot was so top secret that he didn't find out that his character Walter Skinner was in this movie until filming was well under way. He also joked that he could ask for as much money as he wanted as filming took place during the writers' strike, meaning he couldn't be written out.
Gillian Anderson told The New York Times that it was harder than she expected for her to get back into character as Dana Scully to make this movie after five years had passed since the end of Los expedientes secretos X (1993). The Times quoted her as saying, "I walked in thinking, it's going to be like riding a bicycle. It wasn't. It was like riding a unicycle. I'd been trying so hard to stretch myself in other roles, and to catch myself when I did anything that remotely resembles Scully, that when I was put back in the ring with her, my brain started misfiring."
Vanessa Morley: When Fox Mulder and Dana Scully first walk back into the F.B.I. offices right before they walk into the bullpen, a female agent walks by that catches Mulder's attention and he watches her walk away. The woman is the actress who throughout Los expedientes secretos X (1993) played the young Samantha Mulder, and is the same Samantha in the photo Mulder has taped to the back of his home office door.
Joseph Patrick Finn: Producer of many Los expedientes secretos X (1993) episodes is the whispering priest seated next to Father Ybarra during the staff meeting where Dana Scully first mentions using stem cell therapy.
Chris Carter: Sitting on a bench outside of Dana Scully's office. He is holding an urn containing the ashes of his dog, Frankie, who died during filming.