By JOHN PYE AP Sports Writer MELBOURNE, Australia (AP) -- Andy Roddick lunged for a shot by Lleyton Hewitt and felt a sharp pain in his right leg. He stayed down on his hands and one knee for a few seconds, wondering if his Australian Open was finished. He played the next two points, falling behind 3-0 in the second set, before taking a medical timeout to treat his hamstring. Still, Roddick played on. Clearly restricted, he didn't bother to chase down some shots and walked slowly between points with his head down. Finally, after 16 more games, Roddick called it quits. He retired with Hewitt leading the second-round match 3-6, 6-3, 6-4. "It's a miserable, terrible thing being out there compromised like that," Roddick said. The 29-year-old American knew he wouldn't be able to fool an opponent he was playing for the 14th time, one of the few players on the tour older than he is, somebody who was ranked No. 1 before he was and someone with one more Grand Slam title. "He's a tough guy to play," said Roddick, now 7-7 against Hewitt for his career. "You can try to ham and egg it against a lot of guys. But he's really intelligent. He knew what was going on." Roddick's limitations were obvious in the second and third sets. He threw his racket into the wall and argued with the chair umpire over a line call. He bristled when a woman shouted, "Come on Lleyton," just as Roddick was about to serve. "It's frustrating. It's discouraging," he said, referring to the hamstring tendon injury. "You know, your sensible mind says to have a sense of perspective. You still have it pretty good. The competitor in you feels terrible and wants to break stuff." Roddick had his chances. He converted the only break-point chance in the first set and even had opportunities after he injured his leg. But when he knew he needed to win two more sets to advance, he called the trainer, then walked over to shake Hewitt's hand. "I was hitting the ball as well as I could from a compromised position and still felt like I was just hanging on," he said. "I don't know that it would have been smart to do that for two more sets. And if somehow you pull a rabbit out of the hat, I don't think you play in two days. If I'm looking at timelines, I think there's three weeks or so before I have to play again. I like those timelines a lot more than two days." Hewitt, who turns 31 next month, goes to the third round against Milos Raonic, the big-serving, 21-year-old Canadian. If Hewitt eliminates an opponent who has dropped only two service games this year, he could face defending champion Novak Djokovic in the fourth round. Djokovic, who won three of the four major titles last year, kept getting better in his 6-3, 6-2, 6-1 win over Santiago Giraldo. Fourth-seeded Andy Murray, who lost to Djokovic in last year's Australian final, ousted Edouard Roger-Vasselin of France 6-1, 6-4, 6-4. No. 5 David Ferrer beat American Ryan Sweeting 6-7 (4), 6-2, 3-6, 6-2, 6-3, and No. 6 Jo-Wilfried Tsonga downed Ricardo Mello of Brazil 7-5, 6-4, 6-4. No. 2 Rafael Nadal and No. 3 Roger Federer, with 26 Grand Slam titles between them, play in back-to-back matches on Rod Laver Arena on Friday, with defending women's champion Kim Clijsters to play Daniela Hantuchova in a night match on Hisense Arena. Five-time Australian Open champion winner Serena Williams notched her 500th career singles victory Thursday when she beat Barbora Zahlavova Strycova 6-0, 6-4 in the second round. "Five hundred is a lot of matches to play, let alone to win," she said, adding that the left ankle she badly sprained two weeks ago wasn't an issue. "It's totally fine. It was my good ankle, so I'm good." Williams won the Australian Open in 2009 and 2010, but didn't defend her title in 2011 because she was injured. No. 2 Petra Kvitova moved into the third round with a 6-2, 2-6, 6-4 win over Carla Suarez Navarro. Maria Sharapova, one of the three former champions in the women's draw, routed US qualifier Jamie Hampton 6-0, 6-1. No. 7 Vera Zvonareva, a two-time semifinalist at Melbourne Park, No. 9 Marion Bartoli and No. 21 Ana Ivanovic all advanced. For Roddick, this was his earliest Australian Open exit since he first entered in 2002. By not defending points he won at the start of last season, he'll fall in the rankings. He already dropped to No. 14 last year, losing his spot as the top American, after an injury-interrupted season. For a player who hasn't been able to add another Grand Slam singles title since his only major victory at the 2003 US Open, Roddick acknowledges the physical and mentally toll. He had treatment every day in the offseason to get prepared for 2012. He entered mixed doubles at the Australian Open with Williams with the idea of competing at the London Olympics. Mixed doubles is off for now, as he concentrates on returning at San Jose, Calif., next month. Hewitt is still recovering from left foot surgery last year, which restricted him to 20 tour matches and resulted in his ranking plummeting to No. 187. He won the US Open in 2001 and Wimbledon in 2002, but hasn't been back to a Grand Slam final since losing back-to-back in the 2004 US Open and 2005 Australian Open. But he keeps believing he can win. And he paid tribute to Roddick for having the same attitude. "He's similar to me," he said. "He plays with his heart on his sleeve, has that never-say-die attitude as well. It's never easy to play injured or to pull out of a match. It's not a good feeling."