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Dracula opens with a young solicitor's assistant, Jonathan Harker, en route from Budapest into Transylvania, to visit the Castle Dracula and to meet with Count Dracula, a nobleman who has recently purchased an estate in London called Carfax. Harker worries, as he approaches the castle, about the superstitious locals, who seem to fear Dracula. Harker is picked up by a strange driver and taken to the castle, where he meets the Count and begins to discuss business. Harker finds the Count odd—he is active only at night, and seems never to eat. And the Count appears to be the only person living in the Castle.

Harker realizes, slowly, that Dracula was, in fact, the "strange driver" who brought Harker there, and that Dracula is holding Harker prisoner. Harker observes Dracula crawling out his window, along the castle walls, "like a lizard," and even believes he has seen Dracula turn himself into a bat. Harker, in the meantime, stumbles upon a room of the castle in which he meets the demonic forms of three women, who appear to want to drink his blood. But Dracula intervenes, saying Harker is "his," and carries Harker back to his own bedroom. Eventually, Harker decides to escape and finds a deep basement chapel in the castle, where Dracula sleeps in a wooden box filled with earth. Harker attempts to kill Dracula by gashing him in the face with a shovel, but Dracula seems only superficially harmed. Harker escapes from the castle through his window and brings his journal with him, to show his experiences to his fiancée Mina.

Meanwhile, Mina and Lucy, two young, upper-middle-class friends in England, are on vacation at Whitby, an English port. Lucy begins sleepwalking, and Mina finds Lucy one night bent over a rock in a cemetery above Whitby, with a ghastly shade above her. Mina brings Lucy back to her house, and notices, over the ensuing days, that Lucy's condition appears to be worsening. Mina calls in Arthur, a nobleman and Lucy's fiancé, Seward, a doctor and chief of a London insane asylum, and Morris, a Texas man, to help Lucy—Seward and Morris were former suitors of Lucy's, and are now her friends. Seward, realizing he doesn't understand the nature of Lucy's illness, calls in his former Professor Abraham Van Helsing, from Amsterdam, to help Lucy.

Van Helsing believes he knows the cause of Lucy's illness, but does not immediately explain it to Seward and the rest of the group. Lucy appears to be losing blood at night, and in turn Arthur, Morris, Van Helsing, and Seward all give Lucy transfusions to keep her alive. After a while, however, these transfusions prove insufficient. One night, when the men of the group are away, and when Lucy's elderly mother is in her bedroom, a wolf leaps in through Lucy's window, then rushes out—Lucy documents the events in her journal, and her mother dies from the shock of the wolf's attack. Afterward, Lucy cannot be saved by any future blood transfusions, and she dies surrounded by the men of the group.

Meanwhile, Mina has been in Budapest caring for Harker, who has suffered a "nervous breakdown" after his time with the Count, and believes the strange things he saw at Castle Dracula were hallucinations. When Mina and Harker return to England, however, Van Helsing tells Harker that his interactions with the Count were not hallucinations, but real. Van Helsing gathers the men of the group and tells them that Lucy is not truly dead, but is an Un-Dead vampire; the men of the group travel to Lucy's cemetery, observe her haunting the grounds and attempting to suck the blood of children, and later "truly kill" her by stabbing her in the heart with a stake and cutting off her head. Although these events shock Arthur, Morris, Seward, and Harker, the men agree to track down Dracula, whom they believe to have bitten Lucy in England, and "truly kill" him as well.

As the group prepares to do this, however, Harker notices that Mina appears to be getting sick as well, and one night, as the group is all assembled in Seward's office of the insane asylum, a loud crash is heard, and Dracula is seen having bitten Mina and forcing Mina to suck his own blood, while Harker is in a deep trance beside them. This causes the group great alarm, and Mina feels she has been "poisoned" by Dracula in this blood-ritual. In the asylum, Seward has also had conversations with an insane man named Renfield, who speaks of wanting to gain the "life force" of animals he eats, and who is discovered, also, to be communing with Dracula—Renfield allowed Dracula to enter the asylum by inviting him in, and this enabled Dracula to attack Mina and form a "blood link" with her.

The men of the group find out that Dracula has shipped 50 wooden boxes, filled with sacred earth from Transylvania, to England—Dracula needs these boxes to sleep in, to maintain his powers. The group realizes they must sterilize these boxes with holy communion wafers in order to remove their special restorative properties and destroy Dracula. The group finds 49 of the 50 boxes in London, at the Carfax estate and other of Dracula's properties, and sterilizes them; but the last box, they realize, Dracula has taken back to Transylvania. The group tracks Dracula and this final box to Dracula's castle.

The group makes the trip with Mina, who can tell Dracula's location when hypnotized by Van Helsing because of her blood link with the Count. They believe Dracula will land at the port Varna, near Romania, but he actually lands at Galatz—the group intercepts him, however, as he sleeps in his final box en route to the castle, and Harker and Morris stab him in the heart and cut off his head, thus truly killing him—freeing his soul from his Un-Dead body. But Morris is fatally wounded by a gypsy during this attack, and later dies. In a closing note, written seven years later, Harker says that he and Mina now have a child, named after Morris, and that Seward and Arthur both ended up finding love and getting married. They write that they and Van Helsing worry no one will believe their fantastical story of Dracula, even though they have painstakingly assembled their accounts of his activities in order to "prove" his existence.