The Gangreen Gang have been crank calling everyone in town when they decide to go to the next level.
Grubber calls the mayor and pretends to be Miss Bellum, telling the mayor that he has to go do a ribbon cutting at a new mall. When the Mayor leaves, the gang enter his office and get a hold of the Powerpuff Hotline.
The call up the girls and Grubber pretends to the mayor and tells them that Mojo Jojo is up to no good. But when the girls go to his hangout, they see that Mojo is just taking a nap, so they leave.
The gang calls the girls again, this time saying that Fuzzy is causing trouble. But when they find him, he is just taking a bath.
The girls start to think that the mayor is pulling their legs when the phone rings again. They think it's another prank, but the gang tells them that the villain causing trouble is Him and they know that the mayor would never joke about that. But when they meet Him, he is just doing some exercise.
Later, Him, Mojo and Fuzzy call each other up about the girls attacking them for no reason and decide to call the mayor to issue a complaint. Him calls the mayor's office and Big Billy answers and lets it slip that he and the gang have been crank calling the girls into doing stuff. At that very moment, Mojo, Fuzzy and Him burst into the office and fight the gang.
The mayor returns and notices the fight going on and tries to call the girls. But they think it's another prank and hang up.
It is a normal day for the Powerpuff girls. First they help an old lady get her cat out of a tree, then they head to school where they save their teacher from slipping on a roller skate. The Hotline phone rings and they head off to help the mayor open a jar of pickles. Finally, they help the professor in his lab.
While this going on, the girls are being watched by Him through his bath water. He goes on about how he hates the girls and tries to think of a plan to get rid of them. With a little help from his rubber ducky, Mr. Quackers, Him comes up with the perfect plan. In the middle of the night, while all the towns folk are sleeping, Him covers the entire town with a weird red gas.
The next day, the girls see the old lady with her cat stuck in a tree again and decide to help her. But this time, the old lady is all cranky and when Bubbles picks up the cat, it scratches her.
When they head to school, their teacher yells at them for being late and then suddenly, all their classmates and their teacher start throwing stuff at them.
Just then, the Hotline phone rings and the girls head to the mayor's office. They see him with a pickle jar and think he wants it opened. But as soon as they touch the jar, the mayor thinks they're trying to steal it and sicks a SWAT team at them.
The girls try to figure out what is going on. Just then, the narrator tells the girls to shut up and says that they're giving him a head ache.
The girls head home and find the professor with his back turned. When he turns around, he has an angry look on his face and his eyes are bright red and he tries to grab them. The girls run outside, only to see the other towns people on their lawn, all with bright red eyes.
Just then, Him appears and explains what he did. The gas he covered the town with had turned all the people's love for the girls into hate. He then orders the people to attack the girls.
The girls don't really want to fight their friends and loved ones, but Buttercup convinces her sisters that they aren't their friends because they would never harm them, and with that, the girls beat up all the town's people. They tell Him not to do that sort of thing again. Him explains that he never repeats evil plans, but says he will return and disappears.
Later, the girls are at the hospital, apologizing to all the town's people, who are all in body casts, and they quickly forgive them.