Peter is starting to feel sad about all the trouble he has had to endure as both Spider-Man, and Peter Parker. His best friend Harry Osborn has become addicted to drugs, and his close friend Captain George Stacy died in his arms. George Stacy's daughter Gwen Stacy, Peter's girlfriend, wrongly blames Spider-Man for this.
Peter then make a chemical cocktail intended to get rid of spider radiation in his body, thus terminating his spider powers once and for all. Peter takes the chemical and falls into a troubled sleep in which he fights all his enemies, while enduring excruciating side pains. When he wakes up, he notices something different. He has six arms. The potion increased his spider powers rather than destorying them.
He then visits the only man that can help him, Dr. Curt Connors. However, before he fights a vampiric villain called Morbius, the Living Vampire. Although the stress of confronting Morbius makes Connors transform into the Lizard, using an enzyme, Morbius "infected" the Lizard with when he bit him allows Connors to retain his human mind even as the Lizard. In the end, Spider-Man and Connors makes an antidote that turns them both back to normal.