When reports of a humanoid-lizard (naturally dubbed "The Lizard") come out of Florida, Daily Bugle publisher J. Jonah Jameson issues a challenge to Spider-Man: Defeat the Lizard. Hearing about this when Peter goes to prove Jameson to see what Jameson's intentions are, and learns that Jameson only issued the challenge to sell more papers.

Later while at the Natural History Museum with his classmates, Peter takes express interest in the lizard exhibits. When crooks try to rob the museum and take Liz Allen hostage, Peter slips away and changes into Spider-Man and comes to her rescue. Hearing another report of an attack by the Lizard in Florida, Peter decides to take Jameson's challenge. As Spider-Man, Peter pays Jameson a visit to take him up on his challenge, in the hopes that he'd send Peter Parker to Florida to take pictures of the event. The plot works, however it backfires ever so slightly: Jameson himself is going to accompany the boy in order to supervise him.

When they arrive in Florida, Peter makes an excuse of needing to buy film for his camera to get away from Jameson. As Spider-Man, Peter checks out his only lead: Curtis Connors a resident expert on lizards. However, when he arrives at the Connors home, Spider-Man learns from Curt's wife that his husband is the Lizard: That when he was busy trying to find a way to allow humans to grow back limbs. As Connors had lost his arm in the war, he used himself as a guinea pig on the project. While his arm grew back, the side effects of the serum he created caused him to transform into the Lizard.

The Lizard then attacks the Connors home, and Spider-Man defends them. He then works into Connors lab to create an antidote for the serum in the hopes that it can change Connors back to normal. Going into the swamp to find the Lizard, he finds him and his army of obedient reptiles in an old castle. Setting up his camera to take pictures, Spider-Man battles the Lizard and eventually slips him the antidote which changes the Lizard back into his human form.

Connors thanks Spider-Man for his help, and they all decide to keep mum about the fact that Connors was the Lizard, as he had no control over what he did while in that form. Returning to a furious Jameson as Peter Parker, when Peter offers him the pictures (Which he said he bought off a local) Jameson dismisses them as fakes and tears them up. He then tells Parker that this dud of a trip is coming out of his future pay.

Returning back to New York, Peter tries his luck getting a date with Liz Allen, which ends with her hanging up on him because she is expecting a call from that dreamy Spider-Man. As a round up to his adventure to Florida, Peter sends Jameson a mocking letter to the Bugle.

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