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Buso Renkin is the story of teenager Kazuki Muto, who dies trying to save a girl who was being attacked by an eerie monster. The next morning, however, Kazuki is left wondering whether it was all a dream. Lo and behold, the girl, the monster, and his death are all real The girl, Tokiko Tsumura, was actually trying to slay the homunculus (a beast that can take the form of humans, and whose main source of food is people), but Kazuki got in her way. To revive Kazuki, Tokiko replaces his heart with a kakugane, an alchemic device that allows him to summon a lance with which to fight the monsters. It turns out that Tokiko is a member of the Alchemist Warriors, an organization sworn to protect the world from the diabolical creatures. Soon, Kazuki joins Tokiko in her quest to terminate the sinister being that creates and controls the homunculus.

Kazuki and Tokiko find themselves face to face with the legendary traitor of the Alchemist Warriors. The traitor, Victor, has a black kakugane for a heart, giving him the ability to drain energy from any humans in the area and increase his own strength. Then Kazuki discovers that he too has a black kakugane inside him. A fierce battle ensues, pitting the two owners of the rare black kakugane against one another