At a nuclear facility, an officer runs through the hallway. A man on motorcycle, armed with vampire-killing equipment, rides him down. The officer evades him but then Blade comes up to him on foot and they fight. The officer bares his teeth to reveal he's a vampire, but Blade defeats him. The officer reveals they're shipping bodies to Detroit, and someone named Marcus van Sciver is behind the operation. Then Blade decapitates the officer.
A man picks up a prostitute, Nadia, and takes her for a little ride. He takes her to a warehouse with quarantine pens and leaves her there. Then vampires drop out of the ceiling and haul her up into the rafters to feed while the man takes her money.
Blade arrives at a warehouse filled with mannequins and his agent, Shen, says it's their new headquarters. Blade reluctantly agrees.
A boy, Zack Starr, is being taken in a limo by Marcus and other vampires to be transformed. They take him to a dockside complex, then tell him he's been spying on their "House of Chthon," and shoot him dead.
A former soldier, Krista Starr, arrives at her suburban home and is greeted by her happy family. They reveal that her twin brother Zack disappeared a week ago and are interrupted when the police show up to reveal Zack is dead. They take Krista to the morgue where she identifies the body…for the guy who arranged for the prostitute to die earlier. She notices he has a tattoo on his neck but the detective, Brian Boone, dismisses it.
That night Blade hears a news report on Zack's death and goes out on the hunt. He tracks down a tattoo artist who puts the human-servant marks on the vampires' agents and beats him for information.
At Zack's funeral, Krista calls Boone but only gets his answering machine. Later she goes to Zack's apartment and spots someone (Blade) going out the back. After he leaps down several stories, she follows him through the alleyways but loses him. She notices she's bleeding and Blade, on a nearby rooftop, scents the blood and reveals his own fangs.
Krista goes to Boone's office and reveals someone was going through his stuff. When he dismisses her concerns, she sets off the fire alarm then sneaks into his office after the evacuation. She finds a file on her brother and sneaks out with it.
Blade is taking an injection when Shen shows up and talks about the system Blade uses to boost his blood. Then they talk about Marcus and how he's an established businessman and they may have trouble getting close to him.
Krista goes through the files and finds information on a Danny Milano. She tracks him down to an arcade and beats him up for info. She notices he has the same tattoo as her brother but lets him go rather than shoot her. He drops a cylinder filled with ash then runs off to call Marcus' organization while she does an Internet search on the tattoo symbol. It's tied into spontaneous combustion and a researcher named Martin Caylo. She goes to see Caylo, unaware that Blade is following her.
Caylo is protected against vampires and after checking Krista for bite marks, reveals that vampire ash is being used as a drug on the streets to imbue temporary superhuman abilities. He tells her about how the vampires and their agents have infiltrated every level of human society, and he has plenty of proof already. An unsettled Krista takes off.
That evening, Krista is driving when a car slams into her from behind. She goes to check the driver but there's no one there and someone drives off with her car. She hears a voice whispering that he knows who killed her brother, and Krista follows it to a nearby building. She goes into an apartment where vampires disarm her and close in. She manages to grab her gun back and shoot one, but he is unharmed. They go after her but Blade shows up and kills one. The others attack and Krista manages to distract them with well-placed gun shots until Blade can take them out.
Blade tells her to leave and then disappears before she can pursue the matter further. Elsewhere, a truck leaking blood pulls into a slaughterhouse where scientists are pulling strait-jacketed vampires off the ceiling and taking them off to the pens, then performing experiments on them.
Krista meets with Caylo who reveals Blade's background--how when he was delivered by c-section after his mother was bitten by a vampire. Blade roamed the streets until Caylo's friend Whistler took him in. He does give her Blade's old apartment address and she goes there but finds the place in disarray. Then Blade shows up and tells her to let it go but she insists on taking out the ones who killed her brother. Shen calls Blade on his radio earpiece and tells them he's got Van Sciver's location, and then warns Blade not to involve Krista. Blade cuts him off and takes her back to his warehouse.
The scientists are injecting a vampire with an immunity vaccine then expose him to garlic-he bursts into flame.
Blade is testing Shen's new weaponry, and showing off an ultra-sonic projector. They want Krista to infiltrate Van Sciver's organization and try to find out more about his organization, the House of Chthon, and find out what he's up to.
Van Sciver is attending an art gallery opening and Krista tries to get close to him. They flirt a bit as Blade and Shen watch by concealed camera. Van Sciver is just playing with her and reveals he knows who she really is. He taunts her with her brother's death and then lets her go. She goes out to her car and gets some heavy weaponry out of her trunk, then takes off the hidden camera.
As Van Sciver leaves, a waiter gives him a radio headset from Krista. Van Sciver listens in as she draws a bead on him with a sniper rifle and silver bullets covered with garlic. Van Sciver spots her on a rooftop and keeps ducking behind the bystanders while taunting her. Blade heads toward the art gallery while Krista finally starts to pull the trigger, but Van Sciver's female vampire Chase shows up and knocks her out.
Blade arrives on the rooftop to find Krista's duffel bag but no sign of the woman. Krista wakes up to find herself tied to a rack. Van Sciver and Chase show up and he admits he admires her. He takes out a hypodermic and prepares to inject her to transform her, but Chase warns he needs permission. Van Sciver ignores her and gives Krista the injection of his own blood. She passes out and Van Sciver takes her up to the roof and drops her. She crashes onto a car. She has a vision of Zack as a boy and an adult leading her through a playground. Then she finds herself on the shore of a river while vampiric Indians slaughter colonists. She sees Van Sciver as a human demanding that someone kill him.
Finally she wakes up in a body bag and tears her way out. A passing security guard comes in and she starts to attack him, but gets control of herself and flees. She runs out into the rain and Van Sciver shows up to greet her into "the family."
Shen tracks down Krista and Blade suggests if they inject her with the serum they might be able to cure her before the next sunrise if she doesn't make a kill.
Krista wakes up in a dress in one of Sciver's bedrooms, and sees an Indian statue like the one in her vision. Van Sciver greets her and tells her that he "saved" her. He then talks to Chase who warns that the Board won't be happy, but he ignores her.
Blade interrogates Danny then kills him after he directs him to Boone. Chase shows Krista the signs they use to indicate safe locations. Blade puts a tracking unit on Boone's car and follows him while Chase helps Krista to feed on animal blood. Boone picks up another prostitute to feed to the test vampires when Van Sciver arrives and kills her.
Blade approaches the warehouse while Shen prepares his weapons. Boone begs Van Sciver to become a vampire and protests when he sees Krista was transformed. Irritated with his whining, Van Sciver scratches Boone and prepares to feed him to Krista.
Blade discovers the test vampires and they fight and overwhelm him while Van Sciver and Chase leave Boone to Krista. Blade manages to get free and use a UV boomerang (which doesn't work) then the rest of his blades and stakes. Shen's UV boomerang finally goes off, destroying the last vampire. Van Sciver sends his men to deal with Blade and his servant Fritz volunteers to take the newest batch of vaccine.
Blade enters the lab section and finds Krista ripping open Boone's neck. Before he can get to her, the guards attack and Blade fights his way through them. Fritz writhes in pain from the injection then revives and goes to fight Blade. The two fight in the slaughter room and after a brief struggle Blade shoots Fritz with several garlic shells…which have no effect. Fritz wounds Blade but Shen has planted the ultra-sonic unit and activates it. Blade manages to get away but the battery discharges and will take a minute to recharge.
Krista and Chase come after Blade and he tries to hold them off until Shen reactivates the unit. Blade escapes with Krista and injects her with the serum as Shen runs for it. While she collapses on the floor, Blade has to drive off more guards then grabs his motorcycle and escapes as Van Sciver, Chase, and Fritz look on. Blocks away, Blade collapses and Shen shows up to pick him up.
Krista is back with Van Sciver at his house where the "pure bloods" want to meet with him. Before he can leave, Krista asks about the visions of her brother and Van Sciver says she should follow Zack.
Shen and Blade go back to the warehouse with the experiments and find the place torn up. The next night Krista goes to Zack's apartment and then jumps to a nearby building several hundred feet away. She then goes to Zack's grave where Blade grabs her and reveals she can now take the serum twice a day to keep the thirst under control. He asks her to stay in Van Sciver's organization to get him information, and that Zack was working for him as well. She agrees and Shen and Blade wonder if she'll remain loyal to them or switch sides.
And Boone wakes up to find out he has his wish and he's a vampire…but he's the newest "test vampire" in Van Sciver's experiments.