After three days of the top players winning decisively, fifth-seeded Jo-Wilfried Tsonga was upset by Martin Klizan of Slovakia in the second round on Thursday in the first shock of this year's U.S. Open.
The 52nd-ranked Klizan won 6-4, 1-6, 6-1, 6-3.
Before Tsonga's loss, top-five seeds on the men's and women's sides had played 14 matches at this year's tournament - and won all 14 in straight sets.
Later on Thursday, two-time champion Venus Williams was eliminated, losing 6-2, 5-7, 7-5 in the second round to sixth-seeded Angelique Kerber.
Williams, the 2000 and 2001 champion at Flushing Meadows, finished with 60 unforced errors. The match lasted 2 hours, 45 minutes.
She finished the year with only two victories at the Grand Slam events: one at the French Open and one at Flushing Meadows.
Last year, Williams was diagnosed with Sjogren's syndrome, an illness that causes joint pain and fatigue.
Tsonga was the runner-up at the 2008 Australian Open and a semifinalist at Wimbledon this year. He had reached at least the third round in 18 straight Grand Slam trips.
''Today I was not in a good shape,'' he said. ''I didn't play good tennis. It seemed like I couldn't hit the ball enough hard to put my opponent out of position. I don't really know why it was like this today, but sometimes it's happen with me.''
The 23-year-old Klizan, meanwhile, had failed to make it past the second round in three previous Grand Slam appearances. He had never defeated an opponent ranked better than No. 49.
''I had no pressure,'' Klizan said. ''If I lose, then I lose. I lose with (a) good player. But I won and I'm very happy. It means for me more that I beat finally a guy from top 10.''
Top-seeded Roger Federer used a second-round victory in the U.S. Open to work on his net game, winning 32 points from the front of the court in Thursday's 6-2, 6-3, 6-2 victory over Bjorn Phau of Germany.
Federer also finished with 15 aces in a 90-minute victory over his 83rd-ranked opponent.
Federer improved his U.S. Open record to 63-7 and stayed in the mix for his sixth U.S. Open title, which would be a record in the Open era.
Federer's third-round match is against No. 25 Fernando Verdasco.
Serena Williams beat old nemesis Maria Jose Martinez Sanchez 6-2, 6-4 in the second round of the U.S. Open on Thursday.
The 14-time Grand Slam champion overcame six double-faults and 24 unforced errors.
In the 2009 French Open third round, Williams hit a ball she was sure went off Martinez Sanchez's arm, then said the Spaniard cheated by not acknowledging it.
Martinez Sanchez has been ranked as high as 19th but is at No. 108 after struggling with a right thigh injury this year.
The fourth-seeded American next faces 42nd-ranked Russian Ekaterina Makarova.
Jack Sock also reached the third round at a major tournament for the first time. The 19-year-old American beat Flavio Cipolla 6-2, 6-2, 6-4.
Sock, ranked 248th, got in with a wild card. He saved 12 of the 13 break points he faced, while converting all six he earned on the 88th-ranked Cipolla's serve.
Next up is a meeting with No. 11 Nicolas Almagro of Spain, a 6-3, 5-7, 5-7, 6-4, 6-4 winner against Philipp Petzschner.
A week before the start of the Open, Ana Ivanovic couldn't walk without pain in her right foot.
''That's when I started to panic a little bit,'' she said.
Two matches into the tournament, the 2008 French Open champion is feeling healthy - and relaxed. The 12th-seeded Ivanovic and another Serbian former top-ranked player, Jelena Jankovic, have quietly reached the third round at Flushing Meadows. Each has dropped just nine games through a pair straight-set wins.
Ivanovic beat 51st-ranked Sofia Arvidsson of Sweden 6-2, 6-2 on Thursday.
Asked if the torn tendon is fully healed, Ivanovic laughed and said, ''I still have a handful of pills every morning.''
But the foot hasn't been hurting since the tournament started, and Ivanovic's draw is looking fairly painless with Caroline Wozniacki and Francesca Schiavone eliminated in her quarter.
But Ivanovic knows that being the favorite guarantees nothing. In 2008, coming off that title at Roland Garros and at No. 1 in the world, she was stunned by 188th-ranked Julie Coin in the second round here, bothered by a thumb injury. The top-seeded woman had never lost that early in the tournament since the Open era began in 1968.
Ivanovic has been trying to regain her health and her confidence ever since. She has yet to make it back to even a quarterfinal of a Grand Slam event.
''I'm really motivated. I want to get back to the top and back in contention to win Grand Slams again,'' Ivanovic said. ''It's been a long process of getting my mind there and my body and game and everything together. Still, it's going to be a lot of hard work and long process, but I'm starting to enjoy it as well.
''I know if it doesn't happen this week, it's coming.''
It's a similar story for Jankovic, who defeated 115th-ranked Lara Arruabarrena-Vecino of Spain 6-4, 6-2 on Thursday. Both women reached No. 1 in the world in 2008, a breakthrough year for Serbian tennis when Ivanovic won the French, countryman Novak Djokovic took the Australian Open, and Jankovic reached the final at Flushing Meadows.
While Djokovic has since won four more Grand Slam titles, Jankovic lost in the first round at Wimbledon this year.
She's seeded 30th this week - though, as she noted with a laugh, her ranking is now up to No. 27.
Jankovic could face second-seeded Agnieszka Radwanska, one of the top players on the court later Thursday. Then sixth-seeded Angelique Kerber takes on seven-time Grand Slam champion Venus Williams, the juicy second-round match made possible because the American is unseeded after missing time because of illness.
In other women's second-round action Thursday, 13th-seeded Dominika Cibulkova and No. 14 Maria Kirilenko advanced in straight sets.
Kei Nishikori, seeded 17th on the men's side, eliminated American Tim Smyczek.