Aquaman is exposed to a radioactive substance that turns him into a prehistoric sea creature from which he evolved. In order to cure him, Superman and Wonder Woman, inside the Supermobile, are shrunk down to microscopic size and sent within the creature's veins to attempt to give it another dose of radiation in the hopes that it will reverse the effects of the radiation and return Aquaman to normal. In the meantime the rest of the Super Friends have to do whatever they can to limit the creature's destructive nature all over the city.

The Super Friends are visited by Mister Mxyzptlk, who comes complete with a script for a movie that he wants the Super Friends to star in whether they want to or not. The imp uses his Fifth Dimensional magic to cause the Super Friends to act out the script...but Superman is not affected by it. He nonetheless goes along with everything in an elaborate plot to trick Mxyzptlk into saying his name backwards — by using his heat vision to change the last word on the script.