"I've heard about that. I could never do it because I'm so bad at it. So I have to apologize because I have to sing live," she said as the audience roared.
That question was followed with: "I'd love to know what you think of Mitt Romney's promise to fire Big Bird."
"I love Big Bird and I hope no one tells Romney how to get to Sesame Street or Pennsylvania Avenue," she said as the crowd cheered even louder. "He's a good actor. He's a good actor. A chameleon."
That wasn't Streisand's only political moment. The Barack Obama supporter said she taped Thursday night's vice presidential debates and couldn't "wait to go home to watch."
"I'm not going to tell you who to vote for, but ... if you believe in affordable health care and women's rights ... if you want to move forward and not back, you know who to vote for," she said.
Streisand was joined onstage by trumpeter Chris Botti, Italian operatic trio Il Volo and her 45-year-old son Jason Gould, asking him before they sang a duet: "Do you need anything, like, a sweater? You need some chicken soup?"
He earned a standing ovation as his mother looked on, gasping "Oh my God."
She remembered late singer Donna Summer by performing their duet "No More Tears (Enough Is Enough)." She also paid tribute to her late friend — composer Marvin Hamlisch — as she sang "The Way We Were," saying "this is for you" before giving a rousing rendition of the tune.
When she performed "You're the Top," Streisand changed the lyrics, namedropping fellow Brooklynite Jay-Z, who performed eight shows at the Barclays Center last week. She sang lyrics like: "You're a Brooklyn Net, on a private jet" and "it's an accent you can't drop."
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