Case History: A ghastly, green-faced figure scales a downtown highrise building and escapes with a jeweled necklace; fleeing a policeman, he hides in the back of the Mystery Machine, which is parked at the malt shop. He springs out at the gang as they are driving through a short cut and disappears into the fog-shrouded marshes. The gang recognize him as the ghost of Mr. Hyde, a creepy jewel thief that has been haunting the city. The track him to a dilapidated old mansion and fall through a trapdoor into a scientist's lab when they try to follow. There they meet Dr. Jekyll, who tells them a wild story about an experiment-gone-wrong that might be changing him into the ghost of Hyde. He gives the gang permission to look around.

Scooby and Shaggy search the attic, where they find trunks of old costumes—and deduce that someone in the house must have been in show business—but are scared off by Helga, the housemaid, before they can dig any deeper. They are then chased from the library by the ghost of Hyde. Meanwhile, Freddy has found a partially burned newspaper article describing the exploits of Helga the Great and her human fly act. The fleeing Shaggy and Scooby knock Velma down and the three land in the laundry room, where they find that someone has hidden away a pair of muddy shoes and Helga's feather duster. That's enough to send the gang to Helga's room, where they find a can of phosphorus paint and some knockout drops hidden under her mattress. They have just decided to confront Helga when Shaggy appears, claiming to have found something interesting in a fruitbowl in the hallway. But he is instantly grabbed by the ghost of Mr. Hyde and hustled downstairs into the laboratory.

The ghost is intent on turning Shaggy into a frog but is foiled when Scooby charges to the rescue. He and Shaggy elude Hyde (at one point poling through the marsh on the back of an alligator) and hook up with the others; Shaggy shows them the suction cups that he found in the fruitbowl. They then lay a trap for Hyde: Shaggy and Scooby lure the ghost into rooms where the others, themselves disguised as Hyde-lookalikes, spring out at him. Hyde flees toward the backdoor, falls through the trapdoor, and is bustled up in a mattress by Shaggy and Scooby. He is unmasked as Dr. Jekyll, who, after his experiments failed, had decided to turn to a life of crime. When he saw that the kids were onto him, he then planted clues about the house to frame Helga.

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