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The novel opens with the Karamazov brothers returning to their hometown after being raised largely away from home by distant relatives. Now young men, they each have their own reasons for being there: Dmitri seeks to settle an inheritance dispute with their father, Fyodor Karamazov; Alyosha is a novice at the local monastery; and Ivan ostensibly has returned to assist Dmitri. The dispute between Dmitri and his father has been aggravated by their romantic rivalry over Grushenka, despite the fact that Dmitri is already engaged to Katerina Ivanovna. The Karamazovs meet with the elder Zosima at the monastery in an attempt to resolve their differences, but scandal ensues when Fyodor causes a scene.
After the scandal, Alyosha seeks out Dmitri, who is spying on Fyodor from a neighboring garden. Dmitri spills the details of his sordid affair with Grushenka and his shameful theft of Katerina's money in order to woo Grushenka. Leaving Dmitri, Alyosha enters his father's house, where he finds his father, Ivan, Smerdyakov, and Grigory engaged in a religious dispute over dinner. Suddenly Dmitri enters in a rage and beats Fyodor, then runs out the door. After the attack, Alyosha seeks out Katerina, who, to his surprise, is entertaining Grushenka. Grushenka insults Katerina and is thrown out. Katerina's maid hands Alyosha a note, which he opens when he finally returns to the monastery. The note is from Lise Khokhlakov, who declares her love for him.
The next morning, the elder Zosima sends Alyosha to check on his brothers and his father. Alyosha first visits his father, who is angry and suspicions about Dmitri and Ivan. On leaving his father, Alyosha heads off to the Khokhlakov residence, but his journey is interrupted by a group of schoolboys who are attacking another schoolboy. When Alyosha attempts to aid the defenseless schoolboy, the boy bites his hand and runs off. At the Khokhlakovs', Alyosha is taken aside by Lise and proposes marriage to her. After his chat with Lise, Alyosha enters the drawing room, where Ivan and Katerina have a dispute. After Ivan leaves, Katerina gives Alyosha 200 roubles to give to a Captain Snegiryov, who was insulted by Dmitri.
Alyosha heads to the Snegiryovs' cottage, where he meets the entire Snegiryov family, including the young boy, Ilyusha, who bit him earlier in the day. Captain Snegiryov proudly rejects Alyosha's offer of charity. After another brief visit to the Khokhlakovs, Alyosha seeks out Dmitri again. In his father's neighbor's garden, Alyosha meets Smerdyakov, who tells him that Dmitri has gone off to visit Ivan at the village tavern.
At the tavern, Alyosha finds Ivan alone. As they dine together, Ivan defends his religious skepticism to Alyosha by way of a long poetic fantasy entitled "The Grand Inquisitor." At the end of their meal, they part ways.
At this point, the novel shifts to Ivan's perspective. He heads back to his father's, where he meets up with Smerdyakov. Smerdyakov's sly insinuations about a possible murder of Fyodor trouble Ivan. During the night, Ivan finds himself checking on his father for no reason, and feels ashamed. The next morning, Fyodor convinces Ivan to go to Chermashnya, but on the way to the train station Ivan changes his mind and heads to Moscow.
The novel then shifts gears back to Alyosha, who is in the elder Zosima's cell where other monks have gathered to share his last moments. Zosima relates stories from his life and elaborates his religious teachings. Then suddenly he falls to the floor, praying, and dies.
The next morning Zosima's body is put on display at his wake. But despite everyone's expectations that some miracle might occur, his body begins to decay, much to the delight of his detractors.
This scandal troubles Alyosha, and Rakitin, sensing Alyosha's state, invites him to visit Grushenka. Grushenka happily announces to them both that a former lover of hers, a Pole, has finally returned to her, and she awaits his call to join him. Alyosha is grateful that Grushenka has not seduced him and returns that evening to Zosima's wake, where he prays and feels his faith revived.
The novel shifts perspective to Dmitri, who runs around town looking for someone to loan him 3,000 roubles, the amount he stole from Katerina. Both Kuzma Samsonov and Madame Khokhlakov turn him down. Dmitri at first believes that Grushenka is at Samsonov's, but when he realizes that she isn't, he immediately suspects her of going to his father's. Dmitri is tempted to attack his father, but refrains. As he escapes over the garden wall, he is caught by Grigory. In an attempt to free himself, he hits Grigory on the head.
Dmitri returns to Grushenka's, and finally learns from her servants that she is off at Mokroye to meet her Polish lover. He rushes off to Mokroye, where Grushenka rejects her Polish lover and declares her love for Dmitri. They throw a party to celebrate, but the festivities come to an end when officials arrive to arrest Dmitri for the murder of his father.
At this point, the novel moves several months ahead to the days leading up to Dmitri's trial, and turns to the story of Kolya Krasotkin and Ilyusha Snegiryov. After the incident with Alyosha, Ilyusha takes seriously ill. Alyosha rallies the other boys to cheer Ilyusha. Kolya, who was reluctant to visit at first, finally visits Ilyusha with the gift of a dog which Ilyusha was convinced he had killed. Despite Ilyusha's excitement and joy, a Moscow doctor, on a visit paid by Katerina's charitable generosity, announces that Ilyusha has very little time left to live.
Meanwhile Dmitri's case has caused quite a stir throughout Russia, helped in part by Rakitin's sensationalist journalism. Ivan attempts to convince Dmitri to escape a trial he surely can't win, but Ivan's own certainty about his behavior during the murder are put to the test by his conversations with the sly Smerdyakov. In their last conversation, Smerdyakov confesses that he murdered Fyodor. When Ivan returns home after his conversation with Smerdyakov, he imagines that he meets the devil in his own room. The hallucination is interrupted by a visit from Alyosha, who informs Ivan that Smerdyakov has committed suicide.
Dmitri's trial begins the next morning. Just as the witness testimony seems to be going Dmitri's way, Ivan makes a scene at the trial, which in turn stirs Katerina to reveal some damning evidence against Dmitri. Despite his defense lawyer's brilliant closing argument, Dmitri is found guilty.
The novel ends in the days following Dmitri's trial. Dmitri contemplates escaping with Grushenka to America, and Katerina nurses Ivan, who took ill immediately after he caused a scene at Dmitri's trial. Alyosha attends the funeral of little Ilyusha, and the novel closes with Alyosha and his young friends at Ilyusha's wake.