In the Everglades, people started giving weird reports. Something that looked like it was part-lizard, part-man attacked people. Bullets failed to harm it. Lizard became famous all over the nation, and Spider-Man heard about him through the paper(which challenged Spidey to take the Lizard down!). Peter asked Jameson if he could go to the Glades to take photos of the Lizard(and fight him), but was flatly refused. Peter went to the Natural History museum with Liz Taylor and Flash Thompson to learn about lizards and dinosaurs, and Spider-Sensed two criminals stealing a gem. The criminals tried to kidnap Liz while Peter was changing into Spider-Man, but he effortlessly stopped them. Liz was taken with Spider-Man, but Spidey heard a broadcast daring him to fight Lizard and decided to get Jameson to let him go to the Glades. He tied J.J to the ceiling and told him he'd accept the challenge. Jameson called Peter to his office and said he'd need him to go to the Glades to photograph the big fight. In Florida, Parker planned to talk to Dr. Curt Connors, a great herpetologist(scientist who studies reptiles) about Lizard. However, when Peter went to fight the Lizard, he was ambushed. They fought, but Lizard easily hurled Spider-Man a half-mile away. Coincidentally, he saw Dr. Connors' house, with a woman inside crying. He went to warn her about Lizard, but she told him-Dr. Connors was the Lizard. She was gis wife, and she told Spider-Man what happened. Dr. Connors was an Army surgeon who lost his arm in the war. He noticed that lizards can regrow limbs, so he created a formula based on lizard DNA to regrow his arm. It worked on a rabbit, so against her wishes, Connors drank the formula. He quickly regenerated the arm, but it turned him into a human lizard. He fled into the swamp, and although he tried to create a serum to make himself human again, his reptilian mind couldn't do it. Just then, Martha(her name) heard their son, Billy scream. Connors had tried to talk to his son, but Billy was horrified and ran-almost into a snake. Spidey saved him, and Lizard attacked. However, Martha screamed, and it reached the part of human still in him. Lizard slithered into the swamp, and Spider-Man checked his notes. Using Dr. Connors' notes, he created a serum that would make Lizard human again if he drank it. Lizard again attacked unexpectedly, beating Spider-Man savagely and planning to feed his serum to other reptiles to make an army. Spider-Man tracked him down, and saw Lizard surrounded by reptiles that seemed to be obeying him. Both the reptiles and the Lizard attacked Spidey, but he escaped and managed to jam the serum down Lizard's throat. It didn't seem to have an effect. But just as Lizard was about to kill him, the serum worked, changing him back into Curt Connors. Spidey brought him home, changed back to Peter Parker and found a furious J. Jonah Jameson. Although Peter gave him a few photos of Lizard he had snapped, Jameson said they were fakes and ripped them up, also refusing to pay. When Peter got home, he called Liz, but she only wanted to hear from Spider-Man. The issue ends with a prank letter that Spidey mailed arriving at the Daily Bugle and nearly driving Jameson mad.