MASON, Ohio (AP) -- Nearly five hours of tennis in one day caught up with Rafael Nadal, who couldn't keep up with a much fresher Mardy Fish and lost 6-3, 6-4 at the Western & Southern Open on Friday.
Fish's first career win over the second-ranked Nadal sent him into the tournament's semifinals for the second straight year. The American lost to Roger Federer in the title match last year.
Fourth-seeded Andy Murray also reached the semifinals. In the wide-open women's bracket, Maria Sharapova advanced in straight sets.
Nadal's tired legs and burned fingertips had something to do with Fish's breakthrough win.
A day earlier, the 25-year-old Spaniard needed three tiebreakers and 3 hours, 38 minutes to beat Fernando Verdasco. That was followed by a 70-minute doubles match. Plus, his right hand was bothering him - he burned the tips of his index and middle fingers on a hot plate at a restaurant before the tournament began, and had to play with them heavily bandaged.
Fish knew everything was on his side this time in the lopsided rivalry - he'd never come close to beating Nadal in their six previous matches, winning a total of two sets. He kept the ball in play, moved Nadal around the court and waited for his running-on-fumes opponent to make a mistake.
After only a few games on a sunny, 82-degree afternoon, Nadal's green shirt was soaked with sweat. Usually demonstrative on court, Nadal was subdued for most of the match, focused on making it through. He wrapped a towel stuffed with ice around his neck during changeovers and rested it on his overtaxed legs.
Midway through the second set, Nadal had a trainer re-tape his left foot.
Fish is the highest-ranked American on the tour at No. 7. He's the only one who hasn't lost his serve, overcoming four break points against Nadal. He raised both arms when his forehand passing shot from the baseline finished it off.
Fish will play Murray, who advanced with a 6-3, 6-3 win over 10th-seeded Gilles Simon of France. Murray, the 2008 champion, has beaten Simon in seven consecutive matches.
In the injury-depleted women's bracket, the fourth-seeded Sharapova advanced easily with a 6-3, 6-2 win over 10th-seeded Samantha Stosur. Sharapova, who lost in last year's final to Kim Clijsters, won a challenge on match point to improve to 3-0 this year and 9-0 in her career against Stosur.
"I did many good things today that caused her a lot of trouble,'' Sharapova said. "I didn't give her much time to do the things she likes to do.''
Stosur got a day of rest on Wednesday when her opponent, Serena Williams, dropped out of the tournament because of a sore big toe. She got to the quarterfinals, but couldn't get that breakthrough win against Sharapova.
"It's possible to win,'' she said. "I've got to believe that, but I guess it's back to the drawing board.''
The 10th-ranked Stosur was making her first appearance at the U.S. Open tuneup after losing in the final last week at Toronto.
Freelance writer Mark Schmetzer in Mason, Ohio, contributed to this report.