Evan Ross is playing with Trigger, when he notices his dog has gotten larger. He picks up on this, while inside his giant dog's mouth. Evan frantically pleads with Trigger not to bury him in the backyard. Suddenly Evan wakes up screaming in his science class. Mr. Murphy, his science teacher, mocks Evan for having fallen asleep in his class. Evan calls his teacher dumb. Mr. Murphy punishes Evan by forcing him to stay after class to clean out the cage of the class hamster, Cuddles. Evan defiantly walks up to the hamster cage, plucks Cuddles from the wire structure, and hurtles him out the open window. Then that is revealed to also be a dream.
In the hallway after class, Evan is tripped by a bully with the name of Conan Barber. Evan informs the reader that everyone refers to him as Conan the Barbarian. When Evan first arrived to Atlanta, he tried to tell Conan the story of his adventure with Monster Blood. However, Conan declared that he "doesn't tolerate wise guys."
After helping Evan up off the floor, Conan offers him a free punch in retaliation for the tripping. Evan lightly taps Conan with his fist as Mr. Murphy wanders by. Mr. Murphy scolds Evan for taking out his aggressions on innocent classmates and sends him back into the classroom to begin the hamster cage cleaning.
Evan manages to lose the hamster. Eventually he tracks down the little guy and then proceeds on a chase. Cuddles escapes out the window. Eventually Conan catches the hamster and demands that Evan sing a song to get Cuddles back. Mr. Murphy shows up again and repossesses the hamster.
Walking home from his miserable day, Evan runs into Andy. Andy's parents are living overseas for a year. She tells Evan she just arrived at her aunt's and will be starting at his school on Monday. Andy reveals that she has also brought something else with her from home that might help Evan out, it is the old tin of Monster Blood. The two friends examine the empty can in the middle of a forest, only to discover that the can has now magically filled with Monster Blood. Andy and Evan bury the tin in the forest.
Back at home, Evan visits his father, who has been crafting giant abstract sculptures out of sheet metal in the garage. Evan pauses in front of a giant aluminum cylinder that his father calls "the Wheel," which has been accepted into an art competition held at Evan's school. The next day at school, he bumps into Andy in the hall, but can't chat because he is on his way to try out for the basketball team. As soon as he enters the gym, Evan is felled by Conan, who throws a basketball into his face. Biggie Malick, Conan’s friend, tells Mr. Murphy (who is also the basketball coach) that Conan was just tossing Evan's face the ball in a friendly manner.
After practice, Evan shows Andy his hand, which had been crushed by Conan in condolence after he failed to make the team. Andy comes up with a plan to get back at Mr. Murphy: They will dig out the Monster Blood and feed a small bit of it to Cuddles, just enough to turn the hamster into the size of a dog. However, when the two go to retrieve the Monster Blood, they discover it has been swiped, presumably by Conan. Evan accuses Conan of stealing the Monster Blood and Conan retorts by stuffing Evan into a locker.
Andy and Evan decide to break into Conan's house to steal back the Monster Blood. Evan complains that it is too dark to see anything and Andy snaps back that "It usually gets dark at night."
After Conan and his parents leave, the two prepare to sneak inside when Trigger shows up. Leaving the dog outside, the two children sneak in and make their way upstairs to Conan's bedroom. Andy spots the tin of Monster Blood next to Conan's tennis trophies and Evan decides to open the lid and stick his fingers inside. Conan and his parents arrive home while the two children are still inside, forcing Andy and Evan to sneak out the window and cling perilously to the concrete ledge outside. Conan turns on some rap music and begins singing and dancing. Conan's parents then call him downstairs to enjoy some cake and ice cream. Evan and Andy sneak back inside and make their way out of the house.
Andy manages to pull the tin of Monster Blood off Evan's hands and Evan makes Andy promise to bury the Monster Blood. She reluctantly agrees. The next day, Evan stays home sick, so he is quite shocked upon his return to school to see that Cuddles has grown to the size of a rabbit. Evan knows the Monster Blood is responsible, but Mr. Murphy blames Evan for overfeeding him. Evan feels betrayed by Andy, whom he is sure is behind the hamster's growth.
The next morning, Evan sneaks out early to check on Cuddles. As soon as he enters the science room, Cuddles breaks out of the wire cage. Evan thinks quickly and grabs a dog leash, tethering the dog-sized hamster to Mr. Murphy's desk. Evan skips class and meets Andy after school. She admits to having fed Cuddles the Monster Blood and insists she did it as a goof.
Evan meets Andy outside her aunt's early the next morning so the two can check in on Cuddles before class starts, but Andy has to change clothes and they end up arriving at school on time-- just in time to hear Cuddles, who is now ten feet tall, break free of Mr. Murphy's leash. Mr. Murphy tries to hold off the giant hamster like a lion tamer. He brandishes a chair and uses the leash as a whip. Cuddles simply takes the chair from the teacher and chews it to bits. Evan remembers that his father's sculpture is in the gym and it resembles a giant hamster wheel.
Andy and Evan wheel the giant sculpture up to Cuddles, who rather than run on the wheel, tears it apart. Then the giant hamster picks up Conan and prepares to eat him. Evan comes up with a new plan: He will eat some Monster Blood, grow bigger than Cuddles, and then lock him in the supply closet.
Evan and Andy run to her locker, which explodes open with a wave of ever-growing Monster Blood. Evan scoops a big handful of the goop and shoves it into his mouth. He starts to grow and makes his way towards the classroom. He confronts Cuddles, who is now roughly the same size as Evan, and the two start to wrestle. Unfortunately, Evan stops growing and the hamster easily overpowers the 10ft Evan. All hope seems lost when suddenly a loud popping noise is heard and both Evan and Cuddles shrink back to normal size. Evan walks over and easily captures the small hamster. Andy picks up the can and sees that the current date is also the Monster Blood's expiration date.
Evan is hailed as a hero for the way he ate some stuff and Mr. Murphy even rewards him by giving him Cuddles as a present. Andy has also received a present from her parents, a can of Monster Blood they found in Germany. Andy promises she will not use it, but she did already open the tin to sneak a peek. The book ends with Cuddles eating more Monster Blood.
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- This book was never made into a television episode for the Goosebumps TV series. Although, there was an episode called More Monster Blood that was a sequel to the television version of Monster Blood. However, the episode had nothing to do with Monster Blood II, aside from some character references.
- Conan is featured in the episode More Monster Blood.
- This was the first Goosebumps sequel in the series.
- The Dutch version has a few differences from the original book.
- Conan was replaced by a boy called Kevin.
- Cuddles was replaced by "Killer the Rat".
- The Monster Blood was never buried in the forest, but was directly stolen from Mathijs by Kevin.
- Cuddles would become one of the most famous Goosebumps villains after his debut, but would not appear in later Goosebumps books