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Based on unlimited access to the Ultimate Fighting Championship and its rival leagues, Blood in the Cage peers through the chain-link Octagon into the frighteningly seductive world of mixed martial arts, which is exploding in popularity despite resistance from every corner. Wertheim focuses on Pat Miletich, a mixed-martial-arts pioneer and six-time UFC champion, who currently runs the most famous MMA training school in the world.

On June 26, 1976, Muhammad Ali fought in a mixed-rules contest against iconic pro wrestling champion Antonio Inoki for the so-called "martial arts championship of the world." Broadcast from Tokyo to a potential audience of 1.4 billion in 34 countries, the spectacle foreshadowed and, in many ways, led to the rise of mixed martial arts as a major sport.