The prologue shows a church in Guatemala in which two men, Ben Mears and Mark Petrie, are filling small bottles with holy water. When one of the bottles begins to emit an eerie supernatural glow, Mears tells Petrie "They've found us again."The story then flashes back two years, to the small town of Salem's Lot (formally known as Jerusalem's Lot) in Maine in the United States. Ben Mears, an author, has returned to the town after a long absence to write a book about the Marsten House, a ominous old property on a hilltop which has a reputation for being haunted. Mears attempts to rent the house but finds that another new arrival in town, the mysterious Richard Straker, has recently bought it. Straker also opens an antique shop with his oft-mentioned but always absent business partner, Kurt Barlow. Meanwhile, Mears moves into a boarding house in town run by Eva Miller, and develops a romantic relationship with a local woman, Susan Norton. He befriends Susan's father, Dr. Bill Norton, and also renews his old friendship with his former school teacher, Jason Burke. Mears tells Burke that he feels the Marsten House is somehow inherently evil, and recalls how he was once traumatized in the house when he was a child.
After a large crate is delivered to the Marsten House one night, an increasing number of the townsfolk begin to disappear or die in strange circumstances. Both Mears and Straker are initially the main suspects as they are new in town, but it becomes clear that the crate contained Straker's mysterious business partner, Kurt Barlow, an ancient master vampire who has come to the town after having sent Straker to make way for his arrival. Straker kills a young local boy, Ralphie Glick, as an offering to Barlow, whilst Barlow himself kills local realtor Larry Crockett after leaves the home of Bonnie Sawyer being chased out by her husband. The Glick boy then returns as a vampire to claim his brother, Danny, who himself becomes undead. In turn, Danny kills the local gravedigger Mike Ryerson who was bothered by Danny's open eyes and then attempts to kill his schoolfriend Mark Petrie. However, Mark is a horror film buff who manages to repel Danny with a crucifix.
Slowly, the vampires spread as Mears and Burke figure out what is happening to the town and attempt to do something to stop it. Mark's parents are both killed by Barlow, though Mark is allowed to escape when the local priest, Father Callahan, sacrifices himself to Barlow. Jason Burke, however, falls prey to a heart attack following an encounter with the newly vampirised Mike Ryerson. In the end, Susan Norton and Mark Petrie are captured by Straker after breaking into the Marsten House. Armed with wooden stakes and holy water, Mears and Dr. Norton head over to the house to destroy Barlow when they run into Mark who has managed to escape. Inside the house, Dr. Norton is killed by Straker, who is himself then killed by Mears using a pistol. Afterwards, Mears and Petrie find Barlow's coffin in the cellar and destroy him by driving a stake through his heart. They then escape from the other vampires in the cellar (the various townsfolk), and set fire to the house. However, Susan is nowhere to be found. As the house burns, the wind begins to carry the fire towards the town itself. Mears and Petrie then flee Salem's Lot knowing that the fire will drive all the other vampires from their hiding places and purify the town from the evil that has engulfed it.
The story then returns to Mears and Petrie at the church in Guatemala two years later. It becomes clear that are on the run from the surviving vampires from Salem's Lot who have been relentlessly pursuing them. Their supplies of holy water glow whenever a vampire is near. Learning that they have been tracked down yet again, Mears and Petrie return to their lodgings to collect their belongings. However, once there, Mears finds Susan lying in his bed. Now a vampire, she prepares to bite him as he leans down to kiss her, but he drives a stake through her heart. Filled with grief, he and Petrie leave, knowing that other vampires will still be hunting them.
Italiano
Presto Mears sospetta che lui sia il colpevole della sparizione di un ragazzo, Ralphie Glick, che coincide con l'arrivo di Staker in città. Mears intreccia una relazione sentimentale, Susan Norton (Bonnie Bedelia), alla quale rivela la sua sensazione che Casa Marsten sia un luogo maligno. Mears ritrova perfino il suo vecchio insegnante di scuola, Jason Burke (Lew Ayres), e si mostra amico del padre di Susan, il dottor Bill Norton (Ed Flanders). Alcuni strani avvenimenti iniziano ad accadere dopo che due lavoratori, Ryerson e Tibbets, vengono mandati a recuperare una grande cassa da mettere nel basamento di Casa Marsten. La cassa in questione contiene Barlow, il vampiro arrivato a Salem's Lot dopo aver mandato prima il suo 'familiare' Straker in modo da consentire la sua venuta...