The U.S. Open's most stunning loss Wednesday was bigger than just the Grand Slam tournament, with Venus Williams withdrawing and revealing she's suffering from an autoimmune disease.
The seven-time major champion said in a statement that she was recently diagnosed with Sjogren's Syndrome, "an ongoing medical condition that affects my energy level and causes fatigue and joint pain."
The 31-year-old Williams pulled out of two hard-court tuneup tournaments this summer because she was not feeling well. But she came back at Flushing Meadows, and in her first match in two months, Williams beat Vesna Dolonts 6-4, 6-3 on Monday.
She was supposed to play 22nd-seeded Sabine Lisicki in the second round. Instead, the women's field is even more uncertain.
"I think she's a tough girl and I think she'll come back," said Lisicki, who saw Williams on Wednesday wearing match clothing and was surprised to learn she'd withdrawn.
Before the news broke that the older Williams sister was out, Vera Zvonareva was already happy just to advance. In a wide-open women's draw, that counts for a lot - and that became even more true with Williams' exit.
The second-seeded Russian needed three ragged sets to reach the third round, beating 69th-ranked Kateryna Bondarenko 7-5, 3-6, 6-3. With the winners of the last four major tournaments missing from the second round, players with a lot of Grand Slam experience are in short supply. Zvonareva has that, losing in the final at Wimbledon and here at Flushing Meadows in 2010.
"I wouldn't say I'm pleased with the quality of tennis I showed, but I'm pleased the way I handled the match," said Zvonareva, who overcame 46 unforced errors.
A two-time Grand Slam runner-up on the men's side didn't even get started at the Open. Sixth-seeded Robin Soderling withdrew because of illness before his first-round match.
The Swede was scheduled to face qualifier Louk Sorensen in the first round. "Lucky loser" Rogerio Dutra da Silva of Brazil took his spot and made it to the second round, winning when Sorensen retired because of cramps.
Soderling's agent said in a statement that he started feeling "really bad" Tuesday night with stomach pain and a headache, and a doctor recommended he not play.
One American teen pulled a big upset on the women's side, while another couldn't hold onto a lead.
Christina McHale reached the third round of a Grand Slam tournament for the first time, beating eighth-seeded Marion Bartoli in straight sets.
The 19-year-old from Englewood Cliffs, New Jersey, won 7-6 (2), 6-2. She's ranked a career-high 55th and beat No. 1 Caroline Wozniacki in Cincinnati this month.
McHale clinched the victory in style, winning the final point on an ace. The youngest woman in the top 100, McHale was playing in her eighth major tournament.
Bartoli, a 26-year-old Frenchwoman, was a semifinalist at Roland Garros this year. Earlier at that Grand Slam tournament, McHale was up 5-0 in the third set but let it slip away and was beaten 6-7 (4), 6-2, 9-7 by Sara Errani.
McHale didn't lose any leads this time.
"That was a really, really tough loss for me," she said. "But I think it's helped me to learn how to close out matches earlier."
Madison Keys couldn't hold onto several leads in her second-round match, eventually falling to 27th-seeded Lucie Safarova in three sets.
"I must say, she's a very good player for her age," the 24-year-old Safarova said after winning 3-6, 7-5, 6-4.
In her major tournament debut Monday, Keys became the youngest player since 2005 to win a match at Flushing Meadows. At No. 455, she was the lowest-ranked woman in the field.
The 16-year-old from Boca Raton, Florida, won the first five games in taking the opening set. Keys went up a break in the second before letting the lead slip away. And in the third set, she twice broke Safarova only to give the lead back in the following game.
A third American teen, 19-year-old Coco Vandeweghe, lost in straight sets, falling to ninth-seeded Sam Stosur of Australia 6-3, 6-4.
Juan Martin del Potro played here for the first time since winning the 2009 U.S. Open, beating Filippo Volandri of Italy 6-3, 6-1, 6-1. The 18th-seeded Argentine was unable to defend his title last year because of a wrist injury.
"To be playing here after win here, it's special," he said. "It's my favorite tournament, so I'm really happy to take the opportunity to play here again."
Fourth-seeded Andy Murray had a tough first set then cruised the rest of the way, beating Somdev Devvarman 7-6 (5), 6-2, 6-3 in the first round.
Tenth-seeded Nicolas Almagro of Spain lost 6-2, 6-4, 6-3 to 81st-ranked Julien Benneteau of France.
The top-ranked Bryan brothers lost a first-round doubles match at a Grand Slam tournament for the first time since 2001. Unseeded Ivo Karlovic and Frank Moser beat the American twins 6-4, 2-6, 6-2.
Bob and Mike Bryan had won three of the last four major titles, tying the Open era record with their 11th Grand Slam championship earlier this summer at Wimbledon. But they struggled against the 6-foot-10 Karlovic's powerful serve.