Chris Carter's idea for the show was sparked by a report that 3.7 million Americans believed they had been abducted by aliens, the Watergate scandal, and the 1970s series Kolchak: The Night Stalker.

Carter's initial pitch to Fox executives was rejected; he fleshed out the concept and returned weeks later, at which point the pilot was commissioned.

Carter drew stylistic inspiration from the 1988 documentary The Thin Blue Line, the British series Prime Suspect, and The Silence of the Lambs, the latter of which led him to frame the show around FBI agents for plausibility.

Carter deliberately kept Mulder and Scully's relationship platonic at first, basing their dynamic on Emma Peel and John Steed from The Avengers.

Carter initially thought David Duchovny was not particularly intelligent during his audition and asked him to imagine himself as an FBI agent in 'future' episodes, though Duchovny turned out to be one of the best-read people Carter knew.

For the role of Scully, Fox executives wanted an actress who was 'taller, leggier, blonder and breastier' than 24-year-old Gillian Anderson, but Carter insisted she was the only choice due to her 'no-nonsense integrity.'

Mitch Pileggi had unsuccessfully auditioned for two or three other roles on the show before landing the part of Walter Skinner; Carter had been unable to picture him in those roles because Pileggi had a shaved head, and he later grew his hair back and adopted a grumpy attitude that fit Skinner perfectly.

More than 100 actors auditioned for the role of John Doggett, including Lou Diamond Phillips, Hart Bochner, and Bruce Campbell, before Robert Patrick was chosen.

The Cigarette Smoking Man, who became the series' main antagonist, was initially cast merely as an extra in the pilot episode.

Unable to find suitable filming locations in Los Angeles, Chris Carter moved production to Vancouver specifically to access its forests, and the show remained there for its first five seasons before shifting to Los Angeles for budgetary and personal reasons, including Duchovny's desire to be closer to his wife Téa Leoni.

The iconic whistling effect in the show's theme was inspired by the track 'How Soon Is Now?' by The Smiths, and composer Mark Snow ultimately created it using a preset sound called 'Whistl'n Joe' on a Proteus 2 sound module.

The theme's distinctive echo effect was created by accident when Mark Snow, frustrated after several failed revisions, slammed his hand on his keyboard and inadvertently triggered an echo setting that Carter loved.

The opening sequence's unsettling warped face effect was achieved by a video operator Carter found who could create that particular visual distortion, and the sequence went on to win the show's first Emmy Award for Outstanding Graphic Design and Title Sequences.

David Duchovny sued 20th Century Fox before the seventh season, claiming the studio had undersold the show's rights to its own affiliates and cost him significant money; the lawsuit was settled for about $20 million but strained his professional relationships.

The fourth-season episode 'Leonard Betts,' which aired as the lead-out program after Super Bowl XXXI, drew 29.1 million viewers, making it the series' highest-rated episode ever.

The Lone Gunmen trio were originally intended to appear in only one first-season episode ('E.B.E.') but proved so popular that they returned and became recurring characters.