At night on the campus of Empire State University, a shadowy figure scales the wall of the Science Building, and breaks into a lab, while being watched by Blade the vampire slayer. Inside, while Peter Parker burns the midnight oil, the janitor, Jose, makes his rounds. Jose enters the lab where the intruder, a vampire, is injecting himself with some formula. The vampire kills Jose and is soon confronted by Spider-Man. The vampire leaps out the window to evade Spidey, but the hero overcomes the vampire and webs him to a lamppost, while Blade watches from a treetop.
On Riker's Island, the vampire is being held in a cell, bound in a straight-jacket, but he is unable to transform into mist or a bat. Blade, with the aid of allies among the guards, breaks the bloodsucker out. Later, Blade stakes the creature out on the beach under the noonday sun, and tries to extract from him the reason he can survive in sunlight.
That evening, after Jose's funeral, Peter and Mary Jane watch a news report about the jailbreak, and Peter recognizes the image of the suspected accomplice as Blade. Peter decides he has to go to New Orleans, where Blade is based, to get to the bottom of things, and so hitches a ride on a truck bound for Louisiana.
Fifty miles out from New Orleans, Blade transports the vampire, insisting that he will learn the nature of the mutagenic formula his captive injected, whether he cooperates or not. The vampire responds that it is inevitable that vampires will rule humans. At this, Blade loses his temper, stops the vehicle and slashes at the bloodsucker, cursing his kind for taking so many of those he's cared for. The vampire becomes subdued, sorrowfully telling Blade he watched his wife and children killed by vampires.
Later, as the vampire is strapped to a lab table while researchers examine him, Blade becomes curious about his captive's past. The vampire explains he was once Henry Sage, a family man living in Austria in the late 18th Century. He arrived home one night and found his loved ones dead, then was himself attacked by Dracula. As Sage's tale ends, Spider-Man arrives and tackles Blade, asserting that he will see the vampire slayer and the killer of Jose back in jail.
While Spidey and Blade scuffle, Sage makes his escape. The two end their conflict and give chase, tracking Sage to a graveyard. The vampire gets Spider-Man in his clutches and is about to bite him, when Blade hurls his silver knife into Sage's heart. The creature thanks Blade, then disintegrates over the headstones of his family.