"Sanguinarium" was written by newcomers Vivian and Valerie Mayhew and directed by Kim Manners, and is a "Monster-of-the-Week" story, a stand-alone plot which is unconnected to the series' wider mythology.

The show centers on FBI special agents Fox Mulder (David Duchovny) and Dana Scully (Gillian Anderson) who work on cases linked to the paranormal, called X-Files.

In "Sanguinarium", bizarre murders in a hospital's plastic surgery unit lead Mulder and Scully to suspect a supernatural force may be responsible.

During a routine liposuction operation in Winnetka, Illinois, Dr. Harrison Lloyd (John Juliani) suddenly begins to remove so much fat that his patient dies.

Lloyd later tells Fox Mulder (David Duchovny) that he killed the patient because he was possessed; Dana Scully (Gillian Anderson) is skeptical, believing he is only making it up to escape legal consequences.

Mulder inspects the operation room and discovers a pentagram burned into the floor; he begins to suspect that witchcraft might have played a part in the crime.

Meanwhile, staff at the clinic are shocked when another plastic surgeon, Dr. Ilaqua (Paul Raskin), kills an elderly patient by burning a hole through her cheek and neck with a surgical laser, severing her brain stem.

Worried by the events, the clinic's coordinator, Dr. Theresa Shannon, tells Mulder and Scully about a similar series of deaths that occurred there ten years prior.

When Shannon discovers Franklin alone in a blood-spattered operating room, he uses witchcraft to magically teleport surgical tools into her intestines, which causes her to bleed internally.

[3] Prior to having their script picked up by the series, the sisters asked staff writers Glen Morgan and James Wong for writing suggestions.

Carter focused much of the plot on the themes of greed and vanity, and executive producer Howard Gordon developed several graphic scenes.

Like previous episode "Home", Fox Standards and Practices objected to the graphical content, and Carter had to intervene to help retain some scenes.

[6][7] While the Mayhew sisters tried to depict occultism without offending anybody by not connecting Franklin or Waite to any known cult, many Wiccans sent angry letters and e-mails to Fox regarding the portrayal of their beliefs.

David Duchovny stated that "I didn't understand the plot, but I liked the script", noting that Carter and his team improved a weak teleplay and that director Kim Manners "did an excellent job".

"[5] Ultimately, Stegall thought the episode's biggest flaw was its lack of logical writing, and that it required too much suspension of disbelief from the viewer.