- Peter Parker/Spider-Man (First appearance as Man-Spider)
- Aunt May Parker (Main story and flashback)
- Mary Jane Watson
- Dr. Mariah Crawford
- Felicia Hardy
- Daily Bugle
- Detective Terri Lee
- Rich Damsel (First appearance)
- Microchip (First appearance)
- Crusher Hogan (Only in flashback)
- Maria Castle (Photo)
- Frank Castle, Jr. (Photo)
- Lisa Castle (Photo)
After Peter Parker has sprouted four extra arms as a result of his mutation disease, he hides outside the window as his Aunt May comes up the stairs after hearing the noise Peter is making. She goes back downstairs after concluding that she must be hearing things and Peter must be out. After going back inside his bedroom, Peter receives a phone call from Mary Jane Watson suggesting a date, putting him in a difficult situation considering his mutation, having realised that he took the serum too soon against Dr. Mariah Crawford advice. He turns her down but she insists on coming over to sort things out, causing him to flee.
Meanwhile, Punisher saves a young woman named Rich Damsel, who is being held hostage in a warehouse by some thugs, who want her rich father to pay them ransom money. After a fight, he defeats the thugs and prepares to shoot one of them to his death, reasoning that the thug must be eliminated because otherwise he will simply return to a life of crime after getting out of prison. However, the thug jumps out the window before being arrested by the police, while Punisher flees after freeing her.
Elsewhere, Michael Morbius continues to drain the plasma of his victims, and because Morbius disappeared from his hospital room, Spider-Man is declared responsible on the news. In his Battle Van, the Punisher listens to the broadcast and J. Jonah Jameson labelling Spider-Man a criminal who preys on the innocent, and his associate Microchip suggests that he capture Spider-Man. Suddenly, Morbius appears outside his hospital window, and the media mistake him for Spider-Man. Hearing the broadcast himself, Spider-Man arrives to fight Morbius. Punisher also arrives to fight Spider-Man, and succeeds by immobilizing him but Spider-Man escapes and webs up the Punisher, who vows to hunt him down later.
Spider-Man decides to track down Morbius by using the sound recordings of the vampire. However, Punisher is still on his tail and follows him in his Battle Van. Spider-Man arrives at Morbius's hideout, where he is working on a cure for his own mutation, and tries to drain Spider-Man's plasma but stops himself and flies away. Spider-Man gives chase, but Punisher appears and fires a rocket launcher at him, causing him to fall through the roof of a warehouse. As Punisher enters the warehouse, Spider-Man's mutation accelerates and he transforms into a gigantic humanoid spider, the "Man-Spider", and attacks Punisher.