Peter Parker, his best friend Harry Osborn, and secret crush Mary Jane Watson visit a genetics laboratory at Columbia University with their high school class. While taking photos in the laboratory, Peter is bitten on the hand by a genetically engineered "super spider". Feeling unwell, he passes out shortly after arriving home. Meanwhile, Norman Osborn, Harry's father, is attempting to preserve his company's military contract, knowing that its loss will mean the end of his business. He experiments on himself with his company's new, but unstable, performance-enhancing chemical vapor which increases his speed, strength, and stamina. However, it also causes him to become insane and he kills his assistant, Mendel Stromm. The next morning, Peter wakes to find that his previously impaired vision has improved and that his body has metamorphosized into a more muscular physique. At school, he finds himself producing webbing and having the quick reflexes to avoid being injured in a fight with bully Flash Thompson. Peter escapes from the school and realizes that he has acquired spider-like abilities from the spider bite. He quickly learns to scale walls, long jump across building rooftops and swing via webs from his wrists. Lying to his aunt and uncle about where he is going, Peter decides to enter a wrestling tournament to get money to buy a car and impress Mary Jane. During an argument, Uncle Ben advises Peter, "With great power comes great responsibility." Peter lashes out at his uncle and leaves for the tournament. Peter wins, but is cheated out of the contest money. In retaliation he allows a thief to escape with the promoter's gate money. Afterward, Peter finds his uncle has been carjacked and killed. Peter tracks down the carjacker only to find out it was the same thief he allowed to escape earlier. After Peter disarms him, the carjacker tries to get away but falls out of a window and is killed. Upon graduating school, Peter decides to use his abilities to fight injustice, and dons a new costume and the persona of Spider-Man. Peter is hired as a freelance photographer when he arrives in newspaper editor J. Jonah Jameson's office with the only clear images of Spider-Man.
Norman, upon finding out that Oscorp's board members plan to sell the company, attacks them at the World Unity Fair. Although he successfully murders them, Spider-Man arrives and drives him off. Jameson quickly dubs Norman the "Green Goblin". The Goblin offers Spider-Man a place at his side, but Spider-Man refuses, knowing that it is the right thing to do. At the Osborn and Parkers' Thanksgiving dinner, Norman, unknown to Peter, figures out Spider-Man's true identity; the Green Goblin subsequently attacks Aunt May. While Aunt May recovers in the hospital, Mary Jane admits she has a crush on Spider-Man, who rescued her on numerous occasions, and asks Peter whether he ever asked about her. Peter reflects on his own feelings, during which Harry enters. Feeling betrayed by his girlfriend and best friend, Harry tells his father whom Peter loves the most, unintentionally revealing Spider-Man's biggest weakness. The Goblin holds Mary Jane and a tram car full of children hostage on top the Queensboro Bridge where Spider-Man arrives. The Goblin forces Spider-Man to choose who he wants to save, and drops Mary Jane and the children. Spider-Man manages to save both Mary Jane and the tram car, while the Goblin is pelted by civilians showing loyalty to Spider-Man. The Goblin then grabs Spider-Man and throws him into an abandoned building where he begins to beat him [similar to how The Joker's black goon beats up Batman in the 1989 film]. The tables turn as the Goblin boasts of how he will later kill Mary Jane, and an enraged Spider-Man dominates over him, forcing the Goblin into being unmasked. Norman begs for forgiveness, but his Goblin persona attempts to remote-control his glider to impale Spider-Man. The superhero evades the attack, causing the glider to impale Norman instead, and he dies asking Peter not to reveal his secret to Harry. At Norman’s funeral, Harry swears vengeance toward Spider-Man, who he believes is responsible for killing his father, and asserts that Peter is all he has left. Mary Jane confesses to Peter that she’s in love with him, but Peter, feeling that he must protect her from the unwanted attentions of Spider-Man's enemies, hides his true feelings. As Peter leaves the funeral, he recalls Uncle Ben's words about responsibility, and accepts his new life as Spider-Man.
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