The Crime Lords, led by Silvermane, are holding The Kingpin accountable for his failure to eliminate Spider-Man. So six of the Wall-Crawler's greatest enemies are called together to do the job: Doctor Octopus, Mysterio, The Scorpion, The Rhino, The Shocker and The Chameleon. Unfortunately, Spidey's powers have been on the blink due to the changes in his blood chemistry.

The six supervillains can't believe their eyes when Spider-Man walks into their trap at the warehouse. But it's obvious why, when they easily overcome and unmask the fraud. Meanwhile, Silvermane and the Crime Lords grow more disenchanted with The Kingpin and want to put him out of business. Kingpin beats them to the punch, kidnapping Silvermane. Can Spider-Man save the day?

Dr. Mariah Crawford has developed a cure for Spidey's disease, but she's reluctant to give an untested serum to Spider-Man that may result in permanent loss of his powers or worse. But after an angry outburst from Spider-Man, she hands it over. Peter, at the ESU lab, is secretly observed by Michael Morbius, who then swipes the infected blood sample after Peter leaves for the night. Working alone in the campus bell tower with borrowed equipment, Morbius has an accident which will change him forever...

The Punisher comes to New York to deal with the mutating Spider-Man, who has just grown four extra arms, and is in search for also mutated Morbius who is killing (eating) innocent people, and the people of New York blame Spider-Man for all that is happening.

After Spider-Man mutates into the Man-Spider, Dr. Mariah Crawford summons Sergi Kravenoff, better known as Kraven The Hunter, to help her track down Spider-Man and cure him of his mutation with a newly developed antidote. Unfortunately, the Punisher is hot on Spidey's heels. Will the Punisher succeed in destroying Spider-Man in his new mutated form or will Kraven and Dr. Crawford reach him first?

Spider-Man loses his memory and becomes partners in crime with Dr. Octopus. Can a little girl and a cabbie save him?

Deborah Whitman has located Morbius, the Living Vampire, and brings him back to ESU to work on a cure. Just before leaving town, Felicia hears of this and uses the trip as an excuse to stay behind as the Black Cat. Together with Spidey and Whistler, she has to take on Herbert Landon and the Shocker in order to save Morbius from himself.