Spider-Man goes after Eddie Brock for libeling him, as he is now being stalked by bounty hunters at every turn. After being reassured by Mary Jane that he has changed, he seeks help from Dr. Curt Connors who discovers that the suit is alive, and Peter is the host organism.

The Kingpin is furious at Spider-Man and sends the Shocker and the Rhino out to finish him off with the aid of another new invention of Alistair Smythe. Meanwhile, Eddie Brock, as the symbiote creature Venom, is busy playing cat and mouse with Spider-Man, intruding on Peter's private life and making it clear he knows the web-slinger's secret identity. To make matters worse, Peter soon realizes that the pumped-up Eddie as Venom is stronger than he is.

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. However, Kingpin beats them to the punch, kidnapping Silvermane.

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

After a visit from an "old friend" of the family, Peter travels to Russia to investigate the mystery of his parents disappearance, and runs into some old friends.

Still in Russia, Peter discovers that searching for clues to his family's past isn't easy when he has to battle the Insidious Six and the Red Skull.

Spider-Man finds himself in yet another dimension, where he meets himself.