John Singer is a compassionate man, neat and industrious in his behaviors. Orphaned as a child, he was sent to an institution for deaf-mutes, where he learned to read, use sign language, speak, and read lips. However, he does not like to speak except by signing. At 22, Singer meets another deaf-mute, Spiros Antonapoulos, and they become best friends and roommates for 10 years, until Antonapoulos develops a mental illness and is sent away to an insane asylum. Devastated, Singer moves out of their shared home and into a single room in a boarding house, choosing to eat all of his meals at a local café. He wanders the streets at night, feeling lonely and alienated, but gradually begins to develop a network of people who are drawn to him and visit him often in his room. They come to tell him their stories, and although he never answers, they feel he understands what is in their minds and hearts. Singer doesn't really understand them at all and feels only Antonapoulos could ever understand him. When Antonapoulos dies, Singer kills himself.
Mick Kelly is a remarkably responsible preadolescent, caring for her two younger brothers and functioning quite independently in the world at large. However, she is misunderstood by almost everyone who meets her, which is why she finds John Singer such a comforting companion. He seems to listen to her, understand her, and support her dreams of becoming a famous musician although he never responds to her. Mick's sexuality develops as the novel progresses, but she does not enjoy it when she loses her virginity to Harry Minowitz. Her focus is on music and a future far from the small town she is trapped in, and, until the end of the book, she is able to nurture herself by going into what she calls her "inside world" to keep her dreams alive.
Biff is quite kindhearted and quick to help people who are down and out, including any "freaks" who come into his establishment. He keeps his café open at all hours because he knows people need a place to go and because he would miss those who only come in at odd hours. He prides himself on understanding people's natures and is puzzled when he has such difficulty figuring out what draws so many people to John Singer. He does eventually determine the truth of that, however—because Singer never responds, people are able to see Singer as whatever they need him to be. The flaw in Biff has to do with his apparent confusion about love and sexual relationships.
Dr. Copeland is unable to relax and enjoy life. He is constantly driving toward justice for African Americans and thinks he must model the behavior he deems appropriate if they are to better their condition. He looks to scientific and philosophical books for ideas, distrusts all religion, harshly criticizes any behavior that is less than perfect in his eyes, and constantly seethes inside. He works extremely hard as a physician in his community, but he attaches more importance to making people healthy in their thoughts and behavior—which he cannot do—and so he always feels he is failing in his work and mission. He works hard to overcome his bouts of dark, bitter rage, but the tuberculosis attacking his lungs is symbolic of how he is destroying himself by not being able to breathe easily and enjoy life.
When Jake Blount arrives in town he goes on a 12-day bender centered at the New York Café, where Biff Brannon keeps watch over him and is instrumental in helping him to snap out of it. The other person who saves Blount from himself is Singer, who takes him in for a while, perhaps because he is familiar with narcissistic, drunken, mentally ill behaviors because of his years with Antonapoulos. Blount gets a job as the mechanic at the Sunny Dixie Show and then goes to work trying to convert people to his radical ideas. He feels incredibly lonely and alienated in the town, however, and only remains because of his projected connection to Singer. Nevertheless, Blount eventually descends into madness and violence and must leave the town and move on to a new place.