Peter Parker and his college science professor Dr. Curt Conners explore neogenics as a method of limb regeneration. But while experimenting on himself, Connors accidentally becomes the Lizard, a half-man, half-reptile monstrosity that terrorizes Manhattan and subsequently kidnaps his own wife. Spider-Man must stop the Lizard, but his task is doubly difficult because he doesn't want to hurt the good friend he knows is trapped inside.

Dr. Curt Connors is set to study the Tablet of Time, a recently discovered ancient artifact that is said to restore a person's youth. Dr. Connors believes he can cure Spider-Man's mutagenic transformations with the tablet.

With the Tablet of Time, Silvermane's youth is restored, but he continues to grow younger until he finally becomes an infant.

Peter and Mary Jane get engaged. The happy couple goes to ask Dr. Connors if he'll give away the bride, not knowing that he's been fighting against the return of the Lizard. While they are talking to him, three more humanoid lizards attack and kidnap Dr. Connors. With the Lizard taking over and Spider-Man captured, Margaret Connors, Mary Jane Watson, and Debra Whitman will have to save the day.