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Collision Course is a mission in Marvel's Spider-Man. Spider-Man calls Yuriko Watanabe, letting her know that he is planning on visiting the Bowery to make sure Morgan Michaels is safe. After she gives a warning that Silver Sable might shoot him on sight, he agrees to just "be in the neighborhood".

When he arrives, Michaels is nowhere to be found, and it is through a cutscene that players learn he and his guards from Sable International were attacked by the Inner Demons. Michaels is kidnapped with his vial of Devil's Breath, and the Inner Demons escape with him and Mister Negative in an armored vehicle.

Players need to chase down the vehicle while dodging rockets. The chase leads to players underneath the vehicle as it is moving, but as Spider-Man attempts to take Michaels's briefcase, Mister Negative uses his powers on him, and players are taken to a sort of "negative zone", in which the bombing at City Hall is frozen in place.

Here, Mister Negative taunts players about the bombing as they pursue him through the black and white world, insinuating that Norman Osborn knew what was about to happen and ran. When Spider-Man refuses to join him, the fight begins with Mister Negative.

Mister Negative summons wave after wave of "negative" enemies, supposed ghosts of those Spider-Man could not save. Once these are dealt with, players face Mister Negative; similar to other Inner Demons, players must make liberal use of dodge in order to avoid his blasts. Once Mister Negative assembles a mask of energy, players must break it apart to succeed in ending the fight. They need to do this by avoiding a whip enemy and by catching the blasts from the mask to hurl them back.

After re-emerging from the negative world, Spider-Man gets free of Mister Negative and has to forcibly steer the armored vehicle away from pedestrians using his webbing. The truck crashes into a building, and after emerging from the rubble, he finds the Inner Demons have vanished with the Devil's Breath. Silver Sable and their team arrive to take Michaels to safety.

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