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The surprise win of the night was Sean Penn's Best Actor award for his portrayal of Harvey Milk, America's first openly gay politician, in the movie Milk.
"You commie, homo-loving sons of guns. I did not expect this," said Penn, clearly taken aback, as he received the prize.
Mickey Rourke had been tipped to win for his role in The Wrestler, but Penn interpreted his victory as a protest vote by the Academy after California banned gay marriage in a shock November vote.
"For those of us who saw the signs of hatred [from anti-gay protestors] as our cars drove in tonight, I think that it is a good time for those who voted for the ban against gay marriage to sit and reflect on their great shame and the shame in their grandchildren's eyes if they continue their support.
"We've got to have equal rights for everyone," said Penn.
The crowd rose to their feet as Heath Ledger won the Oscar for Best Supporting Actor for his role as The Joker in The Dark Knight, the latest Batman film.
Ledger was 28 when he died last year of an accidental prescription drug overdose, and became only the second actor to win posthumously after Peter Finch for Network in 1977. Ledger's Oscar was accepted by his father, Kim Ledger, sister Kate and mother Sally Bell, on behalf of his young daughter Matilda, who, under Academy rules, is the official recipient.
Penelope Cruz won Best Supporting Actress for her role in Woody Allen's Vicky Cristina Barcelona. "Has anybody ever fainted here?" she asked as she collected her Oscar. "I think I might be the first one."
Hollywood superstar Brad Pitt left empty-handed. His film The Curious Case Of Benjamin Button had led the field with 13 nominations to Slumdog's 10, but collected three minor Oscars, for Art Direction, Make-up and Visual Effects.
Earlier in the evening, the Indian cast of Slumdog Millionaire looked both delighted and overwhelmed as they arrived on the red carpet outside the Kodak Theatre on Hollywood Boulevard beneath overcast skies and the threat of rain.
Azharuddin Mohammed, 10, and Rubina Ali, 9, were flown over for the ceremony from the Mumbai slum in which they live. They got their invitations at the last minute, amid concerns about how they might react to being flown back to the squalor of their tarpaulin-covered homes after exposure to the glitziest night in the LA social calendar.
Some 9,000 miles away, a television set glowed in the tiny, bubble-gum-pink shack Rubina calls home, as her mother, Munni Qureshi, watched the Academy Awards with her three other children asleep on the floor next to her. Shouts of joy erupted in the streets each time the film won.
The film has enjoyed its own a rags-to-riches ride — it was nearly consigned to the straight-to-DVD pile before being saved by Fox Searchlight, which released the film in cinemas.
After the ceremony Boyle said the movie's haul was a victory for independent films. "It’s working against the odds," he said. "We’ve got to protect small films and the studios have to protect them as well."
Gordon Brown, the Prime Minister, hailed a "great night" for Britain in Hollywood. "I would like to congratulate Danny Boyle and all those who worked on Slumdog Millionaire on winning an incredible eight Academy Awards," he said.
"I was lucky enough to see the film myself and understand how it has captured the imagination of people all over the world. Its success is truly well deserved."
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