Charlie boards a jet to Chicago for the psychology conference. He is no longer typing his reports but dictating them into a recorder and having someone else type them. Putting on his seatbelt makes him uncomfortable, and as he searches for the reason, he recalls an event that took place when he was around five years old, before the birth of his sister.
His parents took him to a doctor where he received an alternative therapy to enhance his intelligence. Charlie's father was against the treatments, but his mother was still willing to try anything to help make him normal. Charlie remembers going downtown to Dr. Gaurino's office, being strapped to a black leather medical table, and experiencing a sensory stimulus device that apparently made him black out. Guarino told Charlie that he had nothing to fear and that the treatments would make him smarter. However, Charlie was so frightened he wet his pants. On the way home, Charlie's parents argued about the expense of the treatments and the money she has squandered over the years trying to make Charlie normal. Charlie's father ended up storming out of the house.
As he reflects on the experience, Charlie realizes why he is so motivated to become smarter: it's because this was his mother's constant obsession. Charlie senses that he should resent Guarino's quack treatments, but he doesn't because at least Guarino treated him like a human being. He thinks that Nemur treats him unjustly, and resents the fact that Nemur asserts that he made Charlie what he is today. He places Nemur on the same level as those who constantly made fun of him when he was less intelligent.
When the group arrives in Chicago, a mix-up at the hotel causes them to spend the night at another hotel, where many of the younger conference attendees are staying. To Charlie's surprise he has attained somewhat of a celebrity status, as many of the younger psychologists know of him and the experiment and engage him in questions. Nemur offers an impromptu lecture on Charlie's case to a group in the hotel. Charlie interrupts Nemur's speech, trying to clarify a few points by referring to recent journal articles written in foreign languages, and Nemur becomes upset that he's being grandstanded. It suddenly dawns on Charlie just how little Nemur and Strauss know compared to himself. He begins to view them as nothing more than "ordinary men working blindly." Charlie gets into a discussion with Burt Selden and reveals his negative impressions of Nemur and Strauss, but Burt reminds Charlie that his rapid intellectual growth hasn't allowed him to develop a sense of tolerance. Burt suggests that Charlie meet Professor Nemur's wife, Bertha, a very controlling woman, to get a deeper understanding of why Nemur is the way he is. Though both Alice and Burt have referred to Charlie as a genius, Charlie doesn't think he has yet achieved this level. Charlie rethinks his estimation of those around him, vowing not to view them as inferiors.
Two other professors from Beekman University join Nemur and Strauss for their presentation. The first part of the session is a standard presentation by Dr. Clinger. During this presentation, which Charlie finds insignificant, Charlie fidgets with Algernon's cage. Charlie toys with the idea of letting Algernon loose, but knows that this would disrupt Burt's scientific debut. As part of Burt's presentation on his work with Algernon, Burt reveals that as Algernon's intelligence increased there were times when the mouse would refuse to perform for his food and other times when he seemed to exhibit some self-destructive behavior. When asked if this aberrant behavior was a result of the experiment, Burt sidesteps the question but reveals that none of the other mice exhibited this behavior. In addition, none of the other mice achieved as great a jump in intelligence for so long as Algernon. Charlie is somewhat stunned by this information, recognizing that it has been deliberately withheld from him. The audience is then shown a film depicting Algernon and Charlie's maze races before the operation. Charlie is appalled and angered when the audience repeatedly laughs as the film shows him receiving and reacting to electric shocks as he makes mistakes in the maze exercise. Again, he considers releasing Algernon from his cage. Strauss' presentation is much more clinical, focusing on the details of the operation and the psychotherapy sessions. Charlie becomes upset that most people in the room are thinking of him as a mere subject, a thing Strauss and Nemur have created, instead of as an individual human being. During Nemur's presentation Nemur recounts Charlie's history and suggests that prior to the operation Charlie was in many ways subhuman. This, of course, angers Charlie. Nemur insists that they had corrected a mistake by nature. But as Charlie continues to listen to the lecture, he is hit by a stunning revelation: the experiment is flawed in an important way; the effects might not be permanent because the study didn't account for the tremendous increase in intelligence. Charlie wants to announce his discovery to the entire crowd, but he can't make himself do it.
When it's finally Charlie's turn to speak to the crowd, he releases Algernon from his cage. General chaos ensues as everyone tries to capture the mouse. Charlie laughs at the scene, and Nemur becomes angry; Charlie also informs Nemur that he has made a mistake in his calculations. Charlie manages to capture Algernon in the ladies' room, secretly places the mouse in his pocket, and returns to his room. Charlie decides that he will return to New York; however, he won't go back to his apartment. Instead, he and Algernon will spend several days in the city, and he will get an apartment close to Times Square. The report closes with Charlie commenting that he doesn't think the experiment's flaw is anything critical, but he must seek out his parents soon because he may not have as long as he originally thought.
Charlie's recollection of his visits to Dr. Guarino offers further insight into why he suffers from anxiety in certain situations and why he developed such a strong desire to become smarter. Charlie's ego seems to bloom with the treatment he receives by the younger conference attendees upon his arrival in Chicago, where a celebrity-like status is forced upon him. His assessment that Strauss and Nemur are mere men implies that he feels his intellect has far surpassed theirs.
However, as Burt Selden suggests, although Charlie has made tremendous growth intellectually, his emotional growth remains stunted. One area in particular which remains underdeveloped is that of tolerance. Nemur's insensitive treatment of Charlie, as nothing more than a test subject or something that he and Strauss created, reflects one of the novel's important themes: man's inhumanity to man. Charlie's release of Algernon is a particularly interesting moment, for it foreshadows Charlie's eventual mental decline.