Ishmael begins when the nameless narrator finds a newspaper ad that reads: "Teacher seeks pupil. Must have an earnest desire to save the world. Apply in person" (4).
At first, he is angry, as it reminds him of the counterculture movement of the 1960s, which he participated in only to discover that there was no easy way to save the world.
Nonetheless, he responds to the ad, and finds that the teacher is a gorilla. Behind the gorilla is a sign that reads "With man gone, will there be hope for gorilla?" (9).
The gorilla, named Ishmael, can communicate telepathically. Communicating with him in this fashion, the narrator learns Ishmael’s background - in which the gorilla was stolen from the wild and displayed in a menagerie, then rescued by a Holocaust survivor who taught him his name and how to learn. Impressed, the narrator decides to accept his teachings, returning to Ishmael's office throughout the story.
From this point on, the novel is a Socratic dialogue between the narrator and Ishmael, as they seek to uncover “how things came to be this way” in the world. Ishmael claims that the topic of his teachings is “captivity” (33-34). Having spent the majority of his life in some form of captivity, Ishmael has been able to evaluate the subject to learn that humanity is also living under a form of captivity.
Ishmael learned human language and culture at zoos and menageries, and began to think about the world in a way completely differently than he would have in the wild. The narrator has similar feelings of living in captivity, but has trouble articulating how or why.
Before beginning their discussion in earnest, Ishmael defines some terms:
"Takers" are “civilized" people. They are the descendants of the people who developed agriculture in Neolithic revolution. "Leavers" are people of all other cultures, those considered "primitive" by Takers. A "story" is an interrelation between the gods, man, and the earth. To "enact" is to live so as to make a story true. And finally, a "culture" is a whole people enacting a story together (41).
Ishmael and his pupil establish the differences between the respective stories that the Takers and the Leavers are enacting. To hep understand how Takers pass along their story, Ishmael introduces a figure named Mother Culture, who he insists reinforces the story through every facet of Taker society. Takers assume that humans are the pinnacles of evolution, and that the world was made for man. This belief has led to catastrophic results, yet the Taker story allows man to blame to gods. They believe the gods wishes man to be in control, and so if man is fundamentally flawed, then the gods are responsible for engendering the situation. Ishmael refuses to accept this premise, saying that the only thing wrong with humans is that the story that they insist on enacting puts them at odds with the world.
Ishmael and the narrator also work to establish some immutable laws of life and species that have allowed the world to survive for this long. They agree that a law of limited competition exists amongst all species on Earth, and only man has taken exception to that law. In short, this law suggests that any species may protect and look out for itself, but cannot wipe out another species. A natural food chain must persist.
Ishmael next discusses the Genesis origin stories - of Adam and Eve, and of Cain and Abel - to explore the meaning of the Taker story, and how it historically worked against the Leaver civilizations. He claims that the Fall of Man story was actually developed by Leavers to explain why the Takers started acting as if they owned the world. Adam ate from the Tree of Knowledge, and thereby believed that he had learned “who should live and who should die,” even though he gained no such information (160). What the story represents, then, is the Taker's fallacious belief, in the wake of developing agriculture, that they controlled the Earth, on par with or superior to the gods. The fact that obtaining such knowledge is presented as the fall - and not the ascent - of man supports Ishmael's arguments that Leavers are the first ones to tell it.
Ishmael then explains how the ancient Semitic herders, who originated the tale, used the story of Cain killing Abel to symbolize the way that the agricultural Taker civilizations were destroying the Leavers in order to steal and cultivate their land. The Takers were acting as if they were gods themselves, and had the divine knowledge of who should live or die.
At this point, the narrator is distracted by a visitor and some other issues, and cannot visit Ishmael for several days. When he returns to the office, he finds that Ishmael has been removed, his patroness having passed away. After some investigation, the narrator finds Ishmael in a traveling carnival, and visits him to continue their conversations. Though Ishmael seems sickly, he is eventually willing to continue.
The Leavers only take what they need from the world, and nothing more. Living "in the hands of the gods," Leavers thrive in good times and dwindle in scarce times (229). The Takers, however, insist upon their unique form of agriculture and food surplus, believing that such protection removes them from the whims of the gods and nature. Ishmael points out that Leavers, by living in the hands of the gods, are still subject to evolution, while the Takers have effectively removed themselves from that natural process by acting as though nature does not affect them.
Ishmael summarizes human culture by examining the Leaver story, which provides an alternative story that the Takers could enact. Ishmael claims that the Taker story is not chapter two of the the overall human story, which is how it is seen. Instead, the Leaver story has continued on its own, separate, path. As evolution continues to generate intelligent, self-aware creatures, the Leavers continue to grow, while the Takers have effectively stopped.
Ishmael's final advice to the narrator is that he must spread the world of these lessons, encourage individuals one at a time to break from the thought prison that Mother Culture's story creates. If Takers can begin to enact a different, more harmonious story, then perhaps the world will not be destroyed.
The narrator returns to the city to collect money he can use to buy Ishmael from the carnival. However, he discovers on his return to the carnival that Ishmael has died of pneumonia. He collects the gorilla's belongings, only to discover a message on the back of the poster he had seen on his first visit to the office. The back reads: "With gorilla gone, will there be hope for man?" (263).