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As Congress debates the passing of the Mutant Registration Act, more and more humans find themselves changing, receiving strange abilities, becoming mutants. In Mississippi, a young girl finds herself in this very situation and runs away from home to Canada. Here the young girl, named Rogue, meets a cage fighter named Wolverine and the two flee persecution only to be attacked by Sabretooth and Toad, members of the Brotherhood of Mutants. Cyclops and Storm of the X-Men rescue the two, and bring them back to the Xavier School for Gifted Youngsters to meet Professor Charles Xavier and Jean Grey, who explain the purpose of the X-Men. Meanwhile, Toad and a mutant named Mystique kidnap Senator Robert Kelly, a supporter of the Mutant Registration Act. Bringing him to Magneto, their leader, the Brotherhood turns Senator Kelly into a mutant through a machine Magneto controls.
Soon, an incident at the Xavier School causes Rogue to run away, which the Brotherhood sees as an opportunity to abduct her. After a battle, Rogue is taken by the Brotherhood and brought to their base, where she learns that they intend to use her for their machine. When Senator Kelly arrives at the Xavier School and dies, the X-Men race to save Rogue. The Brotherhood takes Rogue and the machine to Ellis Island and places them in the Statue of Liberty. The X-Men arrive to fight them, but find themselves caught off guard and are quickly beaten, only for them to get their second wind and take down the Brotherhood, saving Rogue and destroying the machine.
After these events, the X-Men learn that Mystique is alive and impersonating Senator Kelly. Wolverine is sent to Alkali Lake in an attempt to learn more about his mysterious past. And finally, Professor X and Magneto meet up in Magneto's jail cell to play chess and discuss the events that are sure to come, for Magneto will continue his fight. But as Xavier says, the X-Men will always be there to stop him.