Peter's professor, Doc Connors, injects himself with reptilian DNA, which slowly changes him into the angry, vengeful Lizard; and since the serum affects Doc Connors' brain, Spider-Man must stop his beloved professor as he begins seeking revenge on those who have harmed him, including Harry.

Spider-Man is out to catch Talon, a female thief who is responsible for high-risk robberies in the city. Things get complicated when Spidey finds out that Talon is his best friend Harry's new girlfriend.

Spider-Man battles Turbo Jet, a modern-day Robin Hood armed with a homemade propulsion system, who steals from the wealthy and gives to the poor. Spidey's life gets even harder as the public rallies around Turbo Jet – and against Spider-Man.

Spider-Man realizes that the diabolical Gaines Twins have brain-blasted him into believing that MJ has died at the hands of Kraven the Hunter. He corners the Twins, but things take a turn for the worse when they once again use their telepathy to trick him.