Sam and Dean take a break from their usual gig to star in a gritty reality show called "Ghostfacers" which chronicles the pursuit of the paranormal. Ed Zeddmore and Harry Spengler have created a radically different and sometimes violent show full of profanity that takes them to the Morton Mansion, an abandoned estate which becomes one of the most haunted places in America one night each year. However, as their team begins to get picked off in grisly manners not fit for television, they realize they are in over their heads.

As time runs out for Dean, Sam convinces him to head to Eerie, Pennsylvania to investigate a possible zombie case. Instead, they discover Doc Benton, a real-life doctor who, in 1816, abandoned his medical practice to follow his obsession with finding the key to eternal life by drugging people and stealing their vital organs. Meanwhile, Bobby finds out where Bela is hiding, and Dean heads out to confront her, leaving Sam behind to deal with the good doctor. Dean and Bela battle it out for the last time, and Dean leaves Bela in a desperate, and possibly fatal, position.