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In the 1960s, geneticist David Banner runs forbidden experiments to create soldiers who can regenerate. When his superiors shut him down, he tests the changes on himself, and his son, Bruce, is born with altered DNA. The Army, led by Thaddeus Ross, closes the lab. Enraged, David blows up the base's reactor and, at home, attacks his family. Bruce's mother dies. David is locked away and the boy is adopted, growing up with no memory of any of it.
As an adult, Bruce is a scientist at a Berkeley lab alongside his ex-girlfriend Betty Ross, daughter of the now-General Ross. They're researching nanomachines that repair tissue. In an accident, Bruce throws himself in front of a colleague and takes a massive dose of gamma radiation. He should die, but he walks away unhurt. A strange janitor starts hanging around the lab. It's David, who reconnects with his son and tells him he's taken samples from him.
All the built-up stress finally blows. Bruce turns into a giant, furious green creature that tears the lab apart. Ross puts him under house arrest and watches everything. Glenn Talbot, a former soldier now working for a weapons company, wants Bruce's DNA to sell. David, for his part, sends three mutant dogs after Betty. Bruce becomes the Hulk again, saves Betty and kills the dogs in a forest.
Ross takes Bruce to a secret desert base, and Talbot tries to trigger the change to take samples. The Hulk breaks out, Talbot dies in the attack and the creature takes on tanks and helicopters in the desert. He leaps miles at a time, hangs onto a fighter jet high in the sky and lands in San Francisco. Betty calms him down and Bruce turns back. Meanwhile, David uses the same technology on himself and gains the power to absorb the properties of anything he touches.
The father asks to see his son one last time. In the conversation, David makes it clear he only wants Bruce's power and electrocutes himself, becoming pure energy. Father and son fight through the air to a mountain lake. Bruce lets his father absorb all of the Hulk's strength, more than he can hold. The Army drops a gamma bomb and David is gone. Ross tells Betty that Bruce is probably dead. A year later, Bruce works as a doctor in the Amazon. When guerrillas try to steal medicine, he warns them in Spanish that they wouldn't like him when he's angry, and his eyes turn green.