Blade (film) has become the vampire hunter Blade. He raids a Los Angeles rave club owned by the vampire Deacon Frost. Police take one of the vampires to the hospital, where he kills Dr. Curtis Webb and feeds on hematologist Karen Jenson and escapes. Blade takes Karen to a safe house where she is treated by his old friend Abraham Whistler (Kristofferson). Whistler explains that he and Blade have been waging a secret war against vampires using weapons based on their elemental weaknesses, such as sunlight and silver. As Karen is now "marked" by the bite of a vampire, both he and
Blade II of the first "Blade movie", Blade has been searching in Prague to find his mentor Abraham Whistler, who was thought to have died after being attacked by Deacon Frost and his vampire pack but instead was turned into a vampire. Blade discovers Whistler being held at a vampire safe house inside an amniotic-like tube. After returning to their headquarters, Blade gives Whistler an anti-virus vampire serum to revert him back to human. Blade's new weapons creator, Scud, express doubts in Whistler becoming human again. Unbeknownst to Blade a pandemic known as the "Reaper virus" has spread through the vampire community.