Japanese outsider Kei Nishikori stole the spotlight on another day of shocks at the US Open on Saturday, while Venus and Serena Williams rolled towards a quarter-final showdown at Flushing Meadows.
Fourth seed David Ferrer was left a punched out wreck as he went down 6-4, 6-4, 3-6, 2-6, 7-5 following an inspired performance by Nishikori.
The 18-year-old made his ranking of 126 look like a mathematical error during the 3-1/2 hour tussle and he kept his nerve to become the first Japanese man since 1937 to reach the last 16 in New York.
"I still can't believe it. I was playing great and he was playing great too. That was the biggest win for me," beamed the 18-year-old, who collapsed on to his back after sealing victory.
He will next face rising Argentine Juan Martin Del Potro, who tamed French 16th seed Gilles Simon 6-4, 6-7, 6-1, 3-6, 6-3.
Rafael Nadal can expect an easy ride into the semi-finals after his draw opened up following the defeats of seventh seed David Nalbandian, ninth seed James Blake and 14th seed Ivo Karlovic.
Argentina's Nalbandian was ousted by 32nd seeded Frenchman Gael Monfils 6-3, 6-4, 6-2 and hard-serving Karlovic was beaten 7-6, 7-6, 6-2 by American Sam Querrey.
Mardy Fish completed a bad night for the seeds when he trampled over fellow American Blake 6-3, 6-3, 7-6.
Andy Murray, the British sixth seed, also looked to be on his way out when he was two points from defeat before he found his range to pull off a 6-7, 4-6, 7-6, 6-1, 6-3 win over Austrian Juergen Melzer.
World number one and Wimbledon champion Nadal, who will not face a top 30 player until at least the semi-finals, blasted into the fourth round by grinding down Serbian Viktor Troicki 6-4, 6-3, 6-0.
While most of the men found it tough going on day six of the season's final Grand Slam, Venus and Serena faced no such problems.
Venus overwhelmed Ukrainian Alona Bondarenko 6-2, 6-1, while younger sister Serena blew past Japan's Ai Sugiyama with an identical scoreline.
"I'm definitely at my best now," seventh seeded Venus boasted after her 56-minute rout under sunny skies at the National Tennis Center.
The 28-year-old, who will next face Polish ninth seed Agnieszka Radwanska, said she has added a little spice to her game since arriving at Flushing Meadows a decade ago.
"I understand the game more," Venus, who has dropped only 11 games in her three matches to date, told reporters. "Trying different kinds of shots too, trying to add some variety."
Neither Venus nor fourth seeded Serena have lost a set during this year's tournament and are the only women left in the draw to have won the U.S. Open previously.
Serena admitted she was "disappointed" at the chance to play Venus in the quarters and not further down the road.
"But I've had over a week to think about it. So right now I'm just hoping to win my next match," said Serena, whose next test will be against Severine Bremond of France.
Four of the top 10 seeds on the women's side have fallen, clearing the way for one of the Williamses to make another title run.
Serena refused to say she was at the top of her game but she appeared close to it during her 66-minute demolition of Sugiyama, where she never faced a break point.
"I'm definitely not at my best but I hope to get there," said the 26-year-old, twice an Open champion who last won the title in 2002.
Dinara Safina, tipped by many as a potential champion here, almost became another big-name casualty before scrapping to a 3-6, 7-5, 6-2 win over Swiss teenager Timea Bacsinszky.
Former world number one Amelie Mauresmo reached the fourth round of a grand slam for the first time in over a year when she won 6-4, 6-4 against Julie Coin, the 188th-ranked Frenchwoman who had earlier stunned top seed Ana Ivanovic.