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"It's going to be a very fun experience," said No 10 seed Isner, who described the chance to play the world No 1 on Wimbledon's main court in the quarter-finals as "pretty special."
After that match, third-seeded Maria Sharapova plays Kim Clijsters in the quarter-finals on the same court. Sharapova, who dropped the first set before recovering to beat No 15-seeded Sabine Lisicki of Germany, 6-7 (8/10), 6-4, 6-3, said she and the Belgian, who plans to retire after the US Open, know each other's games well even though it is their first meeting on grass.
"She's such a tough competitor, such a great mover," said Sharapova, who is herself known for competitive fire. "She has so many great qualities as a tennis champion. It's always nice to face against her, especially at this stage of an event like the Olympics."
Isner is not just looking to experience a moment on the big stage when he plays Federer. While he is 1-3 against the Swiss, he beat him in four sets when they played in Davis Cup in February. Isner said that having the knowledge that he can defeat Federer is critical and that he will go into the match believing that he can win.
Then there is his ferocious serve, a weapon that is especially effective on the fast surface of grass.
Isner had 22 aces, never faced a break point and won 54 of 59 points on his first serve in a 7-5, 7-6 (16/14) win over No 7 Janko Tipsarevic of Serbia in the third round. Isner needed six match points to close the victory, which came when Tipsarevic double-faulted.
Federer endured two rain delays and beat Denis Istomin of Uzbekistan, 7-5, 6-3, and later lost in doubles with Stanislas Wawrinka, with whom he won a gold medal at Beijing in 2008. The four-time Olympian has yet to win a singles medal.
"We know he's got one of the best serves on tour, if not the best," Federer said of Isner, who is 6 feet 9 inches (2.06 meters) tall. "That obviously makes it complicated getting into rallies, into rhythm. That's grasscourt tennis."
Isner said he knew exactly what he needed to do, and not do, against Federer.
"He's the hottest guy on the tour, he's back to No 1 in the world. I'm going to have to serve well," said Isner, who described his form coming into the Olympics as "on a roll", having won seven of his eight previous matches and a title on grass at Newport in the United States.
He had lost in the first round of Wimbledon to Colombian Alejandro Falla, who in turn lost to Federer in the first round of the Olympics.
"I have to go for my shots. Anytime I get a ball I can hit, I'm going to have to hit it big because I can't rally with Roger," Isner said. "It's as simple as that. If I try to get in rallies with him, he's going to beat me."
He said he planned to be aggressive on his service returns, without being "too crazy," and that he didn't stand a chance if Federer took the offence.
Also Thursday, No 1 Victoria Azarenka of Belarus plays seventh-seeded Angelique Kerber of Germany; Serena Williams of the United States plays Caroline Wozniacki of Denmark; and Jo-Wilfried Tsonga of France faces second-seeded Novak Djokovic.
Venus Williams squandered a lead in each set Wednesday and lost her third-round match to Kerber, 7-6 (5), 7-6 (5). Seeking a record fourth gold medal in Olympic tennis, Williams still has a shot with sister Serena in doubles. They play in the quarterfinals Thursday.
Earlier on Wednesday, Serena Williams hit 12 aces and rocketed groundstrokes past No 13-seeded Vera Zvonareva to win 6-1, 6-0. Djokovic beat Lleyton Hewitt of Australia 4-6, 7-5, 6-1. No 3 Andy Murray of Britain rallied past Marcos Baghdatis of Cyprus 4-6, 6-1, 6-4, and will play Nicolas Almagro of Spain.
Four-time Grand Slam champion Clijsters beat former No 1 Ana Ivanovic of Serbia. Clijsters, who is playing in her first Olympics, said retirement was not on her mind and that she was sticking to professional routines honed over nearly two decades of playing
"I've been focusing on my matches," she said. "I'll do that until I play my last match."
