Charlie Gordon is a gentle, happy, thirty-two-year-old with an intelligence quotient (IQ) of 68. For seventeen years, he has worked at Donner’s Bakery, a job his Uncle Herman found for him. He also attends evening classes at the Beekman College Center for Retarded Adults to learn to read and write. His teacher, Alice Kinnian, recommends him for a research experiment on intelligence conducted by Dr. Strauss and Professor Nemur. This experiment, funded by the Welberg Foundation, has already been successful on a white lab mouse named Algernon, so the researchers are ready for a human participant.
Professor Nemur tells Charlie to keep a journal in the form of progress reports for the experiment. The first such “progris riport,” dated in early March, documents Charlie’s illiteracy and strong hope to be selected for the “operashun.” Charlie worries that he will fail the personality and intelligence tests, especially after Algernon beats him when they compete in solving puzzles. He also describes, in a childlike manner, his desire to increase his intelligence to participate fully in discussions and make more friends.
Despite Professor Nemur’s reservations, Charlie is selected to undergo neurosurgery along with enzyme and hormone treatments intended to triple his intelligence. He is nervous about the operation and brings a rabbit’s foot and other superstitious objects with him to the hospital. After the successful operation, he is disappointed that he is not instantly smarter.
Charlie is allowed to return to his job at Donner’s Bakery. In the evenings, Miss Kinnian tutors him, and soon he is beating Algernon in maze races and has learned to read. His intelligence increases rapidly. He is promoted to dough mixer at work and slowly realizes that the people he thought of as friends have been making fun of him. They notice changes in him and become suspicious. Around the time he suggests a few improvements at the bakery, he also catches Gimpy stealing from Mr. Donner. After he confronts Gimpy, the employees band together to have Charlie fired. Only Fanny Birden stands on his side, but while saying good-bye she suggests that something unnatural is happening to Charlie.
Charlie throws himself into reading and spends time at Beekman University pretending to be a student. He also begins remembering childhood events and meets regularly with Dr. Strauss for therapy sessions. In the middle of June, Charlie and Algernon are put on display at the annual psychological association convention in Chicago. His intelligence has surpassed that of both Dr. Strauss and Professor Nemur, and he realizes there is a flaw in their research. This, combined with Nemur’s continual references to Charlie as having been engineered into a human, so upsets Charlie that he releases Algernon, causing chaos. During the distraction, he and Algernon return to New York.
Charlie’s disillusionment leads to self-reflection, and his memories lead him to understand his desire to become more intelligent and his struggle to develop a relationship with Alice Kinnian, to whom he is attracted. Both desires stem from his childhood, when his mother denied that Charlie’s intelligence was low and developed schemes to boost it. Once his sister Norma was born, his mother’s efforts shifted toward getting Charlie institutionalized. He works on finding his parents and sister to attempt reconnecting with them.
Charlie befriends a neighbor, Fay, who helps socialize him. They drink and go dancing. During this time, when memories surface, Charlie recognizes a sort of disassociation, as if a switch has been flipped: At such times, he seems either to watch his own behavior through the eyes of a frightened man with the intelligence of a six-year-old or to watch a developmentally disabled and confused young man through the eyes of a thirty-two-year-old genius.
By late July, Charlie has reached his intellectual peak, and the decline that Algernon is exhibiting begins to show itself in Charlie’s behavior as well. A race begins, as he feverishly works to find the flaw in the experiment before he can no longer comprehend the science involved. By September, Algernon is dead. Charlie reacts violently to his progressive loss of knowledge and rejects Alice, with whom he had finally connected. By mid-November, he asks for his old job back at Donner’s Bakery. He has come full circle. When he accidentally shows up at the Beekman Center and upsets Alice, he decides to leave for the Warren State Home, where he will not have to face anyone who remembers that he was a genius for almost eight months.