At Wellman College, thousands of hamsters overrun the campus, due to the massively obese, yet loving and kind-hearted, professor Sherman Klump, who accidentally releases them. Meanwhile, Sherman has created an experimental formula that reconstructs the DNA of an obese person in a way that allows them to lose weight more easily.
After class, Sherman meets and instantly falls in love with Carla Purty, a chemistry graduate student who is a big fan of his work. After dinner with his obese, impolite family, Sherman asks Carla out on a date, which she accepts, much to Sherman's surprise. The date begins well with Carla showing admiration for Sherman's work, but the club's obnoxious comic Reggie Warrington publicly humiliates him about his weight. Sherman becomes depressed and has a nightmare in which he becomes a rampaging giant and wrecks the city with a single fart that is ignited to cause an explosion. He tests his serum on himself and loses 300 pounds in seconds. Overwhelmed by his thinness, he goes out and buys copious amounts of normal-sized clothing to celebrate, and a $47,000 Viper sports car on his faculty expense account.
To conceal his true identity, Sherman adopts a fake name, "Buddy Love", and invites Carla out on a date at the same club again (while the serum begins to wear off). Reggie is present again and Buddy takes revenge and heckles him mercilessly. Sherman's "Buddy" persona starts to develop an independent personality due to the heightened testosterone levels of the transformation, causing him to be overly assertive and confident. Klump's assistant Jason witnesses Buddy fleeing the scene after he is identified as the person who left Klump's credit card on the bar. Jason follows Buddy and witnesses the transformation back into Klump.
The next morning, Dean Richmond has set up a meeting with wealthy Harlan Hartley at The Ritz to have Sherman explain the serum in the hopes of gaining Hartley's $10 million donation to the science department. However, Sherman arrives at The Ritz as Buddy with Carla. When the Dean spots him, Carla asks Buddy if he will take Sherman's place. He does, and he takes all the credit of his work to Hartley. Hartley and the dean are very impressed, and the dean invites him to the Alumni Ball the next night. Meanwhile, Buddy picks up three beautiful women who seem to idolize him, much to Carla's anger who dumps him and walks out. He then invites the three women back to his place for the night so he can have sex with them.
After the falling out with Carla, Richmond gleefully telling Sherman that Buddy will be taking his place at the Alumni Ball, and seeing a taunting video tape from his alter ego, Sherman has had enough. He and Jason destroy all of the serum samples. Sherman plans to set things right with Carla and get the grant from Hartley. Unfortunately, Buddy knew that this would happen and prepared himself by hiding a sample of the serum in one of Sherman's diet shake cans, which Sherman drinks, causing him to transform into Buddy again. Jason tries to stop him from going to the ball, but Buddy knocks him out with a single blow to the face and departs.
At the ball, Buddy demonstrates the effects of the serum to the audience, but Jason arrives in time, as he has found out that Buddy's testosterone levels are at a lethally high 60,000%. However, Buddy plans to drink a large sums of the potion to get rid of Sherman for good. Jason knows that if he drinks it, it will kill Sherman and possibly Buddy. The two of them get into a brief fistfight, but Sherman begins to fight Buddy from within. However, Sherman eventually transforms into his regular self and admits to the shocked audience, including his parents, of his misdeeds, that Buddy was who he thought he and everybody else wanted him to be, and that he should accept himself for who he is. As he leaves, Carla stops him and asks why he lied; he says he did not believe that she would accept him, but she says it doesn't matter if he is overweight or not. Sherman and Carla share a dance and Hartley gives the donation to Sherman because he is "a brilliant scientist and a gentleman."
What does Sherman use to transform into Buddy?
Serum