MASON, Ohio — Serena and Venus Williams moved into the quarterfinals of the Western & Southern Open by handling the heat, humidity and wind. The conditions were too much for Andy Murray.

Murray’s off-day turned into the biggest upset of the tournament, a straight-sets loss Thursday that left him with hardly any hard-court experience heading into the U.S. Open.

Murray lost 6-4, 6-4 to France’s Jeremy Chardy, an opponent he’d beaten easily the four previous times they’d played. Murray had trouble controlling his shots on a breezy, 85-degree afternoon.

“I was a little bit uncomfortable with those balls bouncing extremely high,” said Murray, who left the court as soon as the match ended and headed directly to the interview room. “It was fairly hard to control.”

Roger Federer, Mardy Fish and Juan Martin del Potro also reached the quarterfinals Thursday.

On the women’s side, Serena Williams won her 19th straight match — her last 12 in straight sets — by beating Urszula Radwanska of Poland 6-4, 6-3. Williams hasn’t lost a set since the Wimbledon final, which she won.

She returned to Wimbledon and won the gold medal in singles and in doubles with sister Venus. The travel and the hot conditions have left her tired.

“I have been playing a lot,” she said. “Definitely (need) more energy. Been traveling a lot, been training a lot. You know, it’s been a really big summer.”

Venus Williams needed a long break between sets while beating Sara Errani 6-3, 6-0. Williams had already played two long matches in the tournament.

Murray left town with a little uncertainty.

He won a gold medal in the Olympics at Wimbledon by beating Federer, the highlight of his career. He went to Toronto last week hoping to get in shape for the hard-court season, but had to withdraw from the Rogers Cup because his left knee started hurting.

Murray felt good and moved well in an opening two-set win on center court Wednesday. Playing on the grandstand court a day later, the Scot never got into a rhythm and repeatedly wasted chances to break Chardy, who had won only one set against him in their four previous matches.

Now, Murray heads to New York to practice for the U.S. Open, having played only three matches on hard courts since returning from Wimbledon’s grass.

“I won’t play any more matches,” Murray said. “When going into the big tournaments, sometimes I’ve won tournaments in the buildup and it hasn’t helped me. This year at Wimbledon, I lost in the first round at Queen’s and made the final there for the first time. I have won Queen’s before and not done well at Wimbledon.

“So it doesn’t normally have that much bearing. But obviously I would have liked to have done a bit better this week.”

Chardy got into the tournament as a replacement for John Isner, who had a sore back. The Frenchman won his opener over Andy Roddick, who developed back spasms during the match on Tuesday.

Federer beat Bernard Tomic 6-2, 6-4 on Thursday and has looked sharp in his two hard-court matches. Federer skipped the Rogers Cup last week.

“I feel like things are working really well for me,” Federer said. “Regardless of what’s going to happen, I’m feeling good, I’m healthy, I have no issues. I’m happy I got over the jet lag, and so the risk is less to get injured and all those things. So I’m in a good place right now.”

Fish, a two-time runner-up at the tournament in suburban Cincinnati, beat Radek Stepanek 6-3, 6-3, his first win over the Czech in five career matches. Fish celebrated his win with a leaping right fist pump after Stepanek’s backhanded drop shot hit the net on match point.

“That was the monkey jumping off my back,” Fish said. “He’s been a tough opponent for me. Not only has he beaten me, but he’s beaten me soundly.”

Fish continues to improve after undergoing surgery in May to repair a heart condition.

“I feel fresher, stronger,” he said. “The summer’s gone well for me as far as getting my match fitness back.”

Serbia’s Viktor Troicki took del Potro to three sets before fading. The Argentine improved to 6-0 in his career against Troicki with a 7-6 (2), 2-6, 6-1 win.

On the women’s side, top-seeded Agnieszka Radwanska overcame an unexpected challenge from wild-card Sloane Stephens before winning 6-1, 4-6, 6-4. Radwanska, who lost to Serena Williams in the Wimbledon final, reached the tournament’s quarterfinal for the first time in three appearances.

Like Murray, she had trouble with the condition on the grandstand court.

“It was so hot and windy,” she said. “I think that this court was slower than the center (court) and the ball didn’t go at all. I was hitting as much as I could, but it just was hard to make winners there.”

Germany’s Angelique Kerber also advanced with a 6-4, 7-6 (5) win over qualifier Andrea Hlavackova of the Czech Republic.