Jelena Jankovic's leg cramped so badly, she couldn't take another step.

Luckily for the No. 2 seed in the U.S. Open, the agony occurred during her post-match run on the treadmill. Anyone who watched could clearly see she left about everything she had out on Arthur Ashe Stadium on Wednesday.

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After Jankovic outlasted Sweden's Sofia Arvidsson 6-3, 6-7 (5), 7-5 she planned to take a 10-minute run on the treadmill but lasted only three when pain flared in the area of a knee injury sustained at Wimbledon.

"I couldn't go anymore," Jankovic said.

"My leg was straight and I couldn't bend it. The muscle was in spasm and I had a lot of pain."

While Jankovic escaped an early exit, No. 8 seed Vera Zvonareva couldn't. Zvonareva was upended by Tatiana Perebiynis of Ukraine 6-3, 6-3 in the tournament's biggest upset yet. Svetlana Kuznetsova shook off an early break and rallied to a 7-6 (3), 6-1 victory over Sorana Cirstea of Romania.

Fifth-seeded Elena Dementieva advanced over Pauline Parmentier of France 6-2, 6-1, but No. 25 Francesca Schiavone was knocked out by Britain's Anne Keothavong 6-2, 3-6, 6-4, and Zheng Jie of China eliminated No. 26 Anabel Medina Garrigues 6-1, 6-4. No. 12 Marion Bartoli of France, No. 14 Victoria Azarenka of Belarus and No. 15 Patty Schnyder of Switzerland also won. Former champ Lindsay Davenport, the No. 23 seed, beat Alisa Kleybanova of Russia 7-5, 6-3.

In men's first-round play, No. 3 seed Novak Djokovic shook off an injury to his left ankle in the third set and beat Arnaud Clement of France 6-3, 6-3, 6-4. Djokovic rolled the ankle while going for a shot on the right sideline in the fourth game. After receiving on-court treatment, he wrapped up the match with a break of Clement's serve.

Eighth-seeded Andy Roddick, who has battled a shoulder injury this summer that led him to skip the Beijing Olympics, beat Fabrice Santoro of France — the oldest man in the draw at 35 — 6-2, 6-2, 6-2.

Fifth-seeded Nikolay Davydenko beat Dudi Sela of Israel 6-3, 6-3, 6-3; Jo-Wilfried Tsonga, the No. 19 seed, moved on with a 6-7 (3), 6-4, 6-2, 6-3 win over Santiago Ventura of Spain; No. 18 Nicolas Almagro beat Frank Dancevic of Canada 6-3, 6-4, 7-5; and Dmitry Tursunov, the 26th seed, upended Eduardo Schwank of Argentina 7-5, 4-6, 7-5 7-6 (5).

Treatment with ice and stretching and massaging loosened Jankovic's leg enough for her to go back to the locker room to take a shower before she spoke to reporters in a much more comfortable setting.

Until then, it was Arvidsson who made her life difficult for the better part of three hours.

The combination of not being in match condition following the injury and an array of hard forehands and well-placed drop shots by Arvidsson left Jankovic fighting to get her wind during the 2-hour, 44-minute match.

"That was a really tough one," said Jankovic, who has reached the fourth round in the first three Grand Slam events this year. "As you can see, I am completely out of breath. She really pushed me to the limit."