Charlie Gordon, a mentally retarded thirty-two-year-old man, is chosen by a team of scientists to undergo an experimental surgery designed to boost his intelligence. Alice Kinnian, Charlie’s teacher at the Beekman College Center for Retarded Adults, has recommended Charlie for the experiment because of his exceptional eagerness to learn. The directors of the experiment, Dr. Strauss and Professor Nemur, ask Charlie to keep a journal. The entire narrative of Flowers for Algernon is composed of the “progress reports” that Charlie writes.
Charlie works at Donner’s Bakery in New York City as a janitor and delivery boy. The other employees often taunt him and pick on him, but Charlie is unable to understand that he is the subject of mockery. He believes that his coworkers are good friends. After a battery of tests—including a maze-solving competition with a mouse named Algernon, who has already had the experimental surgery performed on him—Charlie undergoes the operation. He is initially disappointed that there is no immediate change in his intellect, but with work and help from Alice, he gradually improves his spelling and grammar. Charlie begins to read adult books, slowly at first, then voraciously, filling his brain with knowledge from many academic fields. He shocks the workers at the bakery by inventing a process designed to improve productivity. Charlie also begins to recover lost memories of his childhood, most of which involve his mother, Rose, who resented and often brutally punished Charlie for not being normal like other children.
As Charlie becomes more intelligent, he realizes that he is deeply attracted to Alice. She insists on keeping their relationship professional, but it is obvious that she shares Charlie’s attraction. When Charlie discovers that one of the bakery employees is stealing from Mr. Donner, he is uncertain what to do until Alice tells him to trust his heart. Delighted by the realization that he is capable of solving moral dilemmas on his own, Charlie confronts the worker and forces him to stop cheating Donner. Not long afterward, Charlie is let go from the bakery because the other workers are disturbed by the sudden change in him, and because Donner can see that Charlie no longer needs his charity. Charlie grows closer to Alice, though whenever the mood becomes too intimate, he experiences a sensation of panic and feels as if his old disabled self is watching him. Charlie recovers memories of his mother beating him for the slightest sexual impulses, and he realizes that this past trauma is likely responsible for his inability to make love to Alice.
Dr. Strauss and Professor Nemur take Charlie and Algernon to a scientific convention in Chicago, where they are the star exhibits. Charlie has become frustrated by Nemur’s refusal to recognize his humanity. He feels that Nemur treats him like just another lab animal, even though it is disturbingly clear that Charlie’s scientific knowledge has advanced beyond Nemur’s. Charlie wreaks havoc at the convention by freeing Algernon from his cage while they are onstage. Charlie flees back to New York with Algernon and gets his own apartment, where the scientists cannot find him. He realizes that Nemur’s hypothesis contains an error and that there is a possibility that his intelligence gain will only be temporary.
Charlie meets his neighbor, an attractive, free-spirited artist named Fay Lillman. Charlie does not tell Fay about his past, and he is able to consummate a sexual relationship with her. The foundation that has funded the experiment gives Charlie dispensation to do his own research, so he returns to the lab. However, his commitment to his work begins to consume him, and he drifts away from Fay.
Algernon’s intelligence begins to slip, and his behavior becomes erratic. Charlie worries that whatever happens to Algernon will soon happen to him as well. Algernon eventually dies. Fearing a regression to his previous level of intelligence, Charlie visits his mother and sister in order to try to come to terms with his past. He finds the experience moving, thrilling, and devastating. Charlie’s mother, now a demented old woman, expresses pride in his accomplishments, and his sister is overjoyed to see him. However, Rose suddenly slips into a delusional flashback and attacks Charlie with a butcher knife. He leaves sobbing, but he feels that he has finally overcome his painful background and become a fully developed individual.
Charlie succeeds in finding the error in Nemur’s hypothesis, scientifically proving that a flaw in the operation will cause his intelligence to vanish as quickly as it has come. Charlie calls this phenomenon the “Algernon-Gordon Effect.” As he passes through a stage of average intelligence on his way back to retardation, Charlie enjoys a brief, passionate relationship with Alice, but he sends her away as he senses the return of his old self. When Charlie’s regression is complete, he briefly returns to his old job at the bakery, where his coworkers welcome him back with kindness.
Charlie forgets that he is no longer enrolled in Alice’s night-school class for retarded adults, and he upsets her by showing up. In fact, Charlie has forgotten their entire romantic relationship. Having decided to remove himself from the people who have known him and now feel sorry for him, he checks himself into a home for disabled adults. His last request is for the reader of his manuscript to leave fresh flowers on Algernon’s grave.
Charlie's "friends" laughed at him because he was cognitively impaired, and in the beginning, he wasn't really sure why so he just laughed along with them.