Told through a series of "progress reports" written by the main character Charlie, Flowers for Algernon examines the potential for science to benefit humanity, as well as cause considerable harm. The novel also offers a critique of the treatment of the mentally disabled. After undergoing an experimental surgery, Charlie, who was mentally disabled, sees his IQ triple. With his higher intelligence, Charlie is able to live a full adult life. But, the effects of the surgery prove to be temporary and Charlie soon returns to his initial intelligence level.
The short story and the novel share many similar plot points, but the novel expands significantly on Charlie's developing emotional state as well as his intelligence, his memories of childhood, and the relationship with his family and Miss Kinnian.
The story is told through a series of journal entries written by the story's protagonist, Charlie Gordon, a man with a low IQ of 68 who works a menial job as a janitor in Donner's bakery. He is selected to undergo an experimental surgical technique to increase his intelligence. The technique had already been successfully tested on Algernon, a laboratory mouse. The surgery on Charlie is also a success, and his IQ triples.
Charlie falls in love with his former teacher, Miss Kinnian, but as his intelligence increases, he surpasses her intellectually, and they become unable to relate to each other. He also realizes that his co-workers at the bakery, whom he thought were his friends, only liked him to be around so that they could make fun of him. His new intelligence scares his co-workers, and they start a petition to have him fired, but when Charlie finds out about the petition, he quits. As Charlie's intelligence peaks, Algernon's suddenly declines—he loses his increased intelligence and mental age, and dies shortly afterward, to be buried in a metal box in the backyard of Charlie's home. Charlie discovers that his intelligence increase is also only temporary. He starts to experiment to find out the cause of the flaw in the experiment, which he calls the "Algernon-Gordon Effect". Just when he finishes his experiments, his intelligence begins to regress to its state prior to the operation. Charlie is aware of, and pained by what is happening to him as he loses his knowledge and his ability to read and write. He tries to get his old jobas a janitor back, and tries to revert to normal, but he cannot stand the pity from his co-workers, landlady, and Ms. Kinnian. Charlie states he plans to "go away" from New York and move to a new place. His last wish is that someone put flowers on Algernon's grave.
The novel opens with an epigraph taken from Book VII of Plato's The Republic :
Any one who has common sense will remember that the bewilderments of the eye are of two kinds, and arise from two causes, either from coming out of the light or from going into the light, which is true of the mind's eye, quite as much as of the bodily eye.
Charlie Gordon, 32 years old, suffers from phenylketonuria and has an IQ of 68. He holds a menial job at a bakery which his uncle had secured for him so that Charlie would not have to be sent to a state institution. Wanting to improve himself, Charlie attends reading and writing classes at the Beekman College Center for Retarded Adults; his teacher is Miss Alice Kinnian, a young, attractive woman. Two researchers at Beekman, Dr. Nemur and Dr. Strauss, are looking for a human test subject on whom to try a new surgical technique intended to increase intelligence. They had already performed the surgery on a mouse named Algernon, dramatically improving his mental performance. Based on Alice's recommendation and his motivation to improve, Charlie is chosen over smarter pupils to undergo the procedure.
The operation is a success, and within the next three months Charlie's IQ reaches 185. However, as his intelligence, education, and understanding of the world increase, his relationships with people deteriorate. His co-workers at the bakery, who used to amuse themselves at his expense, are now scared and resentful of his increased intelligence and persuade his boss to fire him. One night at a cocktail party, a drunken Charlie angrily confronts his scientific mentors about their condescending attitude toward him, particularly Dr. Nemur because Charlie believed that more than anyone Dr. Nemur considered him nothing more than another laboratory subject and not fully human before the operation. Charlie also embarks on a troubled romance with Alice. Unable to become intimate with the object of his affection, Charlie later starts a purely sexual relationship with Fay Lillman, a vivacious and promiscuous artist in the neighboring apartment.
When not drinking at night, Charlie spends weeks continuing his mentors' research and writing reports which include observations of Algernon, whom he keeps at his apartment. Charlie's research discovers a flaw in the theory behind Nemur and Strauss's intelligence-enhancing procedure that could cause him to revert to his original mental state. His conclusions prove true when Algernon starts behaving erratically, loses his own enhanced intelligence, and dies.
Charlie tries to mend the long-broken relationships with his parents. He remembers that as a boy his mother insisted on his institutionalization, overruling his father's wish to keep him in the household. Charlie returns after many years to his family's Brooklyn home and finds that his mother now suffers from dementia. Although she recognizes him, she is mentally confused. Charlie's father, who had broken off contact with the family many years before, does not recognize him. Charlie is only able to reconnect with his now-friendly younger sister, Norma, who had hated him for his mental disability when they were growing up, and is now caring for their mother in their newly depressed neighborhood. When Norma asks Charlie to stay with his family, he refuses but promises to send her money.
As Charlie regresses intellectually, Fay becomes scared by the change and stops talking to him. However, Charlie attains sufficient emotional maturity to have a brief but fulfilling relationship with Alice, who cohabits with him until the extent of his mental deterioration causes him to order her to leave. Despite regressing to his former self, he remembers that he was once a genius. He cannot bear to have his friends and co-workers feel sorry for him. Consequently, he decides to go to live at the state-sponsored Warren Home School, where nobody knows about the operation. In a final postscript to his writings, ostensibly addressed to Alice Kinnian, he requests that she put some flowers on Algernon's grave in Charlie's former backyard.