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The tragedy of Medea begins in medias res (in the middle of things). Medea's Nurse bemoans Medea's fate—she has been abandoned with her two young children by her husband, Jason, who has married the Princess, daughter of Creon, king of Corinth. In the midst of her lamentations, the Nurse recounts how Jason left his homeland, Iolocus, in a ship called the Argo to find a treasure called the Golden Fleece. The Golden Fleece was guarded by a dragon in Medea's homeland, the Island of Clochis. Aphrodite, goddess of love, made Medea fall in love with Jason and then help him to steal the Golden Fleece. While she and Jason were fleeing Clochis by boat, Medea killed her brother so that those pursuing them would have to stop and bury his body. In Iolocus, she and Jason hatched a plot to steal rulership from the king, Pelias. Medea managed to trick Pelias' daughters into killing him by promising that, if they did, she could restore him to his youth. She did not restore him, and Jason and Medea were chased from Iolocus to Corinth, where they lived as exiles.

Medea is infuriated by Jason's abandoning her and their children, and makes threats to kill Creon and the Princess. These threats reach Creon at the palace where the children's Tutor overhears that Creon intends to exile Medea from Corinth. He tells the Nurse what he heard outside Medea's house. The two promise not to tell Medea. The Nurse says she fears for the children and doesn't like the way Medea has been looking at them. She sends the children inside where, from offstage, Medea addresses them, saying she wishes they were dead and cries aloud in her grief. The Nurse and Tutor leave and the Chorus of Corinthian women assemble outside Medea's house, saying that it heard Medea cry. Medea comes out to speak to the Chorus of her troubles. Soon, the king, Creon, arrives to give Medea her sentence of banishment. He tells her he fears she will cause him and his daughter harm. She tries to convince him she is harmless, but he will not relent. Eventually she manages to get him to agree to give her a single day in which to plan where she and the children will go in their exile. When Creon is gone, Medea laughs at him and calls him a fool for allowing her to stay. She intends to punish Creon, the Princess, and Jason for the way they have mistreated her.

Next Jason comes to offer Medea money and letters of recommendation to ease the burdens of her exile. The two of them argue about Jason's behavior, and Jason contends, somewhat ridiculously, that he is acting in Medea and the children's best interest. Medea calls him a coward and refuses any help. Jason leaves. When he is gone Medea reveals her plot to kill the princess with a poisoned dress and crown, and then, in order to hurt Jason most, to also kill her own (and Jason's) children. But first she must find a place of refuge for after she leaves Corinth. Her friend, Aegeus, the king of Athens, soon arrives on his way from the oracle of Phoebus whom he has consulted concerning his inability to have children. Medea promises him that she will help him to have children if he promises to shelter her from her enemies. He agrees and exits.

Medea sends a member of the Chorus to fetch Jason back. When he comes, she tells him he was right and she is only a foolish woman and begs him to find some way to let the children stay. She sends the children with Jason to the palace to give the Princess the dress and crown as gifts. They go.

The Tutor soon comes from the palace with the children and with the good news that the children are allowed to stay. Medea grieves because, for her, it means the Princess is dead or dying and she must complete her plan by killing the children. A Messenger arrives from the palace and recounts the Princess and Creon's death in vivid detail. The Princess died putting on the gifts, and Creon died by becoming entangled in the poisoned dress after embracing his daughter's corpse. Medea relishes the news and steels herself to murder her children. She takes them offstage (inside) and we hear them struggle. Jason comes to the house and commands his men to undo the bolts of the door. Before he can manage, Medea appears over the stage in a chariot drawn by chimeras sent by the sun god, Helios, her grandfather. She has with her the dead bodies of her children. She and Jason exchange cutting remarks about the tragic events, and the Chorus concludes the play by saying that sometimes, rather than expected events, the gods bring unexpected things to pass.