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Leon's campaign in Resident Evil 6 begins at Ivy University located in Tall Oaks. A university by the same name is also featured in an earlier Capcom game, Phoenix Wright: Ace Attorney: Trials and Tribulations where its location was never stated. Both being games developed by the same company, this is unlikely to be a coincidence.
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In the Urban Chaos map for Mercenaries you can find an arcade with old Capcom games such as Star Gladiator, SonSon, Ghosts'n'Goblins and Darkstalkers.
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You can use the slide and ride the panda in the playground near the beginning of Chapter 3 with Chris & Piers. You can also use the slide as Ada in her campaign, but curiously only Chris can ride the panda.
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One of the death scenes when killed by a zombie is a reference to the original Resident Evil game, specifically to the point where you meet your first zombie eating Kenneth J. Sullivan.
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In Leon's campaign, you rescue a rookie cop caught in a town filled with zombies on his first day at work. This is a throwback to how Leon was in a similar situation back in Raccoon City. The gas station in this scene, Stagla, is also a reference as one was located in Raccoon. A miniature of this station is also seen in the Special Features menu of the game.
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In the original Japanese release, several references to the 9/11 terrorist attacks against the United States, and the war on terror, were included in Adam Benford's letter to Leon Kennedy regarding the foundation of the Division of Security Operations. When localized, these references were removed.
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Sherry's letter to Claire mentions a person named "Ronny" who would be excited to see Claire. This, however, is a mistranslation as the name in the original Japanese version is "Rani-chan". This is most likely referring to Rani Chawla, from the CG movie Resident Evil Degeneration, who already has ties to Claire.
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According to Yoshiaki Hirabayashi, the producer of Resident Evil 6, the idea to use Albert Wesker in the game came up at least once. Spoiler:Due to Wesker being dead, however, they couldn't use the character but still wanted to somehow involve him in the story. As they were developing the character of Jake Muller at the time, they came up with the idea of him being Wesker's son.
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Chris Redfield was originally meant to die in Resident Evil 6 Spoiler:instead of Piers, but the developers decided to swap the characters because they felt Chris's death would have been cheap and tacked on simply for shock value.
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Carla Radames was originally going to be a clone of Ada Wong, but the producers of the game told the developers they weren't allowed to incorporate cloning into the story. The team originally came up with the idea that there could be 4 to 5 Ada clones, and that in the game it would be revealed that every Ada the player has encountered in the series thus far had been different clones of her.
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The Elephant Killer is a nod to the Handcannon in Resident Evil 4, where if the player tends to buy the weapon, the merchant will ask Leon: "Stranger, what you need that for? Going huntin' an elephant?"
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