Io enters wearing the horns of a cow. She asks where she is, complains about the ghost of Argos pursuing her and the gadfly stinging her, and asks why Zeus tortures her in this way. Prometheus addresses her by name and shows knowledge of her wanderings. Io asks Prometheus to reveal who he is and why he is being punished and, once he has done so, she asks him to tell her of the rest of her wanderings. The Chorus interrupts, asking that she first tell them how her wanderings began. Io recounts how in dreams she kept hearing a voice telling her to go give her virginity to Zeus. An oracle warned her father Inachus to throw her out or face Zeus's wrath, and he did as he was ordered. Io was immediately transformed, in body and mind, into a cow, and a gadfly and the shepherd Argos, who was soon killed, followed her. She has been wandering ever since.
The Chorus expresses their horror at this story. Prometheus recounts some of Io's further adventures, taking her through East until she comes to Asia, constantly avoiding dangerous peoples who live on the way. Io asks what reason she has to go on living, but Prometheus says that she should be glad not to have his fate, since he cannot die and must suffer much longer. He tells her, however, that a son greater than him will depose Zeus. Asked if Zeus can avoid this, Prometheus answers that this may happen only if a descendant of Io frees him. Prometheus goes on to prophecy Io's remaining wanderings, where she will pass through Africa past other strange peoples and various monsters. Prometheus next recounts Io's wanderings to date in order to demonstrate that his prophetic gift is trustworthy. Finally, he says that Io's journey will end when Zeus will restore her to her human form and impregnate her with a gentle touch. At least he tells of Io's descendants, the Danaids, fifty women who choose to kill their husbands rather than marry cousins. One of them is swayed by love not to kill, and she gives birth to the kings of Argos. Eventually, one of her descendants, known for archery, Heracles, will free Prometheus.
Io runs off, again struck by madness and stung by the gadfly. The Oceanids lament her fate, saying that nothing good can come of marriages between those of unequal rank. They express their hope that none of the Olympians ever take an interest in them, since they can't imagine and way of escaping Zeus.
Aeschylus uses Io's entrance to emphasize the intertwining of her destiny with that of Prometheus. Io laments her fate in a five verses and Prometheus responds in kind with five verses of his own. The literary symmetry here is intended to underscore the relation of the two characters. The following conversation between them reveals first, the prophesy of Zeus's downfall, which would profit both Prometheus and Io, and then the prophesy that Io's descendant will free Prometheus. In other ways, too, Prometheus and Io are bound together by fate. The former is a victim of Zeus's hatred, while the latter is a victim of his love. As a tyrant governing by arbitrary laws, Zeus harms everyone in his path. Io's account of her sufferings leaves Hera out of the picture. She tells in great detail of how Zeus attempted to seduce her in his dreams and how he had her cast out of her father's house. When she speaks of her transformation into a cow and her pursuit by Argos and the gadfly, Io suddenly becomes somewhat vague on the details. This may be because her transformation into a cow has made her more scatter-brained. But there is clearly a literary purpose at work here. Both Argos and the gadfly were sent by Hera, the jealous wife of Zeus, and Zeus turned Io into a cow to escape Hera's detection. Though Hera is mentioned in the context of Io's fate, responsibility for her condition is clearly placed on Zeus. Aeschylus wants to place Zeus at the forefront in order to make him the tyrant solely responsible for Io's suffering just as he is responsible for Prometheus's punishment.
The lengthy travelogues describing Io's wanderings serve to situate the action of the play in both space and time. Io travels East and South. Most scholars believe that the sequel, Prometheus Unbound, features a similar travelogue as Prometheus revealed the future wanderings of Heracles, taking him to the West and North. Together, these travelogues charted the entire known world, circumscribing the universe within which the struggle between Zeus and Prometheus takes place and creating a backdrop for the conflict. Furthermore, the story of Io's journey and her descendants would have had significance for Greek audiences that it may not have for us. Prometheus explains that Io's wanderings are the reason for the names Bosporus and Ionian Sea, which the audience was familiar with. Io's descendants, in turn, rule over the city of Argos, and spawn the hero Heracles. The adventures of Heracles were already within the realm of recent history for the ancient Greeks, while the city of Argos existed and the stories of its past kings were known. By referencing the familiar place names and historical figures, Aeschylus brings this story of remote and ancient gods closer to the everyday reality of his audience.
The travelogue here also shows the dual nature of Prometheus's gifts to humanity. We have already seen that several characters make the somewhat ironic reference that although he knows how to counsel others, Prometheus cannot free himself. The chorus has likened him to a "doctor who has fallen sick." Prometheus must wait until the time is right; until then, his gifts to humanity cannot help him and are the cause of his torture. Those gifts endanger others, as well. Io learns of Zeus's lust for her through dreams, and her father exiles her on the command from an oracle. Divination has led Io to her wanderings, but it was Prometheus who taught divination to humanity. She is threatened on her path by weapons of all sorts, and these weapons spring from the technology Prometheus has given to humanity. The gifts that help can also be used to harm.