Mulder and Scully investigate a bizarre death in which their very own boss, Assistant Director Walter Skinner seems to be yet again the prime suspect. Poor man!

The episode starts when, Jane Brody a mail sorter sneaks into the employer's rest room to smoke a cigarette. Suddenly, thousands of bees swarm into the room with her and before she can escape they sting her to death.

Back in Washington, an E-Mail message is sent to Mulder detailing the incident that has just occured but for some reason, Skinner intercepts it and deletes it. Acting even more suspicously, he then incinerates Brody's body and destroys any evidence of the bee attack. He then goes over to a forensics lab in Virginia identifying himself as Agent Fox Mulder and switches a container of Brody's blood with another fake container. When he is just about to leave, he is approached by Det. Ray Thomas (the man who sent Mulder the E-Mail) who thinks he is really Mulder. Skinner tells him that the evidence does not warrant any further involvement in the case.

Later, Mulder pays Skinner a visit saying that someone has destroyed all evidence of the bee attack ever reaching him and that Det. Thomas was found executed by a gunshot. While Scully undergoes tests for her cancer at a hospital, Skinner asks Mulder to help him solve a mystery. At night, Skinner is approached by Cancer Man who Skinner accuses of killing the detective. The Cancer Man replies saying that he had "failed to neutralize a potentially compromising situation".

After investigating the theft of evidence, Mulder discovers that someone stole Brody's body, switched her blood and also killed the detective with a gun issued to someone within the government. Meanwhile, Skinner finds that his own gun is missing so he goes to visit the rest room where Brody was killed to try to find some evidence. He finds a bee hive in the top corner of the room so takes a piece of it to an entomologist for analysis. While still investigating, Mulder also finds that on one of the video surveillance cameras, there is a man seen talking to Det. Thomas just before he is killed but it is unclear who it is so he takes it to a photo unit to try to find out who Thomas's killer is.

While the entomologist is analysing the hive he disturbs some more bees which quickly swarm him and kill him. Mulder arrives at the crime scene and discovers that he had died of smallpox so concludes that someone must be using the bees to spread the disease. Skinner questions Brody's co-worker who tells him that a damaged package was taken by investigators working on the same case. She also tells him that students at a school were attacked by bees so Skinner rushes to the hospital and tells them that they should be treated for smallpox, not bee stings.

The surveillance footage clearly shows that Skinner was the one talking to the detective so Mulder accuses him of working with the Cancer Man all along. Skinner though insists he was framed. Skinner meets with the Cancer Man firing several shots at him in a result of his anger.

Later, in a scene reminiscent of the final scenes in Sleepless and Wetwired, the Cancer Man accompanied by other members of his secret organization, tell Marita Covarubbias (Mulder's latest informant) to tell Mulder what he wants to hear. So it seems that all three people that Mulder has worked with or trusted have been secretly working covertly with the Cancer Man. It puts new emphasis on the words 'Trust No One'.