The Lizard heads to Dr. Connor's lab to find a formula to transform reptiles into his personal army...
This issue begins with Spider-Man walking across a "web bridge" he has built himself and recalling his last fight with the Lizard. All of a sudden he hears a noise from around the corner, and goes to investigate what it is. He sees a truck being high-jacked by some thugs, and swings down to stop them. Spidey manages to beat both the crooks despite that one of his arms is sprained from last issue. He then goes back to the rooftops and continues using web bridges to go around town, as its easier than web swinging with his one arm.
Meanwhile, on the other side of town, Martha Connors is in bed when she hears the sound of a window being opened. The Lizard is sneaking into Curt Connors' laboratory, as he is looking for a formula to turn people into human reptiles. Unfortunately for the Lizard though, he can't understand the scientific notes, and so smashes all of Curt's beakers and lab equipment. The Lizard then leaves Curt's apartment so he can find Curt Connors and force him to give him the formula (The Lizard doesn't realise that he is Curt Connors.) Back in the apartment, Billy wakes up when the beakers smash. Martha calms him by claiming the wind knocked them over, but in her mind she can't help but feel worried since her husband is a monster.
The next morning, at the Daily Bugle, Frederick Foswell is about to leave to tail Peter Parker so he can find out how he gets so many good photos of Spider-Man. However, he is called back by Jonah and told to work on a story about the Lizard. Jonah then turns his gaze to Betty Brant and Ned Leeds, who are working on their wedding plans. Jonah yells at them nevertheless. Once Jonah's turned away, Ned and Betty go back to their wedding plans.
Meanwhile, back at Peter's house, he tries hiding his injury by putting his hand in his pocket, but its too painful. He then decides that he might as well wear his sling, and claim that he hurt his arm on his motorbike. He takes a bus to Empire State University, where he runs into Flash Thompson and Harry Osborn. Flash teases Peter and asks him if he's pretending to be Spider-Man, but once Peter tells his lie, Harry says he guessed that happened all along. Flash then leaves to get a cup of coffee with Gwen. Harry also tells Peter that Gwen is throwing a party for Flash, which annoys Peter since she didn't tell him herself because she thought he was dating Mary Jane.
At a seaside resort, Aunt May is asked by another holidayer what New York must be like with menaces like the Lizard rampaging about. Aunt May frets about Peter for a moment, then remembers she doesn't have to worry about him since he isn't a "wild teenager".
However, despite what Aunt May thinks, Peter is out web-swinging at that moment, looking for the Lizard. After looking for hours in locations such as sewers, Spidey decides to check out the zoo, just in case. At first Spidey is disappointed that the Lizard isn't there, but then he sees a poster advertising the world's largest collection of reptiles. Peter works out that this is why the Lizard stayed in New York. Forty-Eight minutes later, at the train tracks, Spider-Man's spidey sense tingles, meaning the Lizard is nearby. Spidey tries to leap and stop the Lizard before he can see him, but the Lizard turns around in time to stop him. Spidey punches the lizard repeatedly simply to distract him, although he knows that it is useless. The Lizard knocks Spidey back with his tail, whilst taunting Spidey that he can't beat him since he can only use one arm.
Spidey is knocked to the ground and the Lizard grabs a piece of the train tracks to attack Spidey with. Spider-Man manages to make him drop it by punching it, but the Lizard simply hits him with his fists, then picks him up and throws him into the train, almost knocking Spider-Man out. The Lizard decides to save his strength and smashes the train open. Out of the train carriage the Lizard smashed, snakes and crocodiles all come out, ready to attack Spidey since they're being controlled by the Lizard. Spidey webs up a crocodile's jaws, but is unsure about if he'll be able to do the same for all the reptiles.
Back at Mary Jane's house, Mary Jane tells her aunt Anna that she's going out for a while. Mary Jane escorts Anna over to Peter Parker's house before leaving, but Anna is surprised that Peter isn't home.
At the train tracks, it looks like Spidey will be defeated by the reptiles, as they are starting to overwhelm him. However, he gets an idea, and grabs the tail of one of the crocodiles, and uses the crocodile as a giant whip to keep the others at bay. When he realises that his reptiles have lost, the Lizard jumps onto the train which is heading to the Florida Everglades.
Spider-Man jumps on the train after him, but is almost knocked off by the Lizard's tail. He jumps up and kicks the lizard, whilst thinking that he finally has worked out how to beat the Lizard. Spidey then starts taunting the Lizard and making him follow him. Running along the train, all the while mocking the Lizard, Spidey finds the right train car he was looking for, and climbs in. The Lizard thinks he won because Spidey has trapped him, but Spidey tells him that he (the Lizard) is the one who's outsmarted himself. Spidey then starts attacking the Lizard so that the Lizard won't realise where he is and smash the sides of the carriage to escape. During their fight, the Lizard starts to get slower and weaker, and eventually is knocked out. Spidey had tricked him into following him into a refridgerator car, thereby sapping his strength.
To make sure the extreme cold won't kill the Lizard, Spidey wraps him up in a web cocoon. He then stops the train and gets the train workmen to flag down a train so that he can return to New York. After a while, Spidey returns to Curt Connor's lab with the unconscious Lizard still in the web cocoon. Spidey starts making the serum to turn him back to the Lizard, but is interrupted by Martha Connors knocking on the door, asking if its Curt. Spider-man tells her that its him, and that they shouldn't get their hopes up in case he can't change the Lizard back to Curt. Just before he gains his full strength, Spidey feeds the Lizard the formula, yet is still unsure as to whether he will be Curt or the Lizard. Martha and Billy are panicking behind a door, wondering what is happening, until a moment later the door opens and Curt is in the lab. Curt thanks Spidey then Spidey leaves.
In a street, a few minutes later, Peter Parker passes by Mary Jane and Harry. They offer him a ride but Peter declines. Peter makes his way home, depressed that even though the Lizard's been defeated, he still hasn't got money to pay for Aunt May's trip and that he hasn't been studying.
Meanwhile, at the Connors apartment, Curt wonders if they could do something to help Spidey in return for what he's done for them, but they assume someone like him has everything someone would need.