An injury-hit Serena Williams crashed out of the Australian Open against Ana Ivanovic Sunday, missing the chance for an 18th major title and a rare calendar-year Grand Slam.
As men's champion Novak Djokovic reached the quarter-finals with his 28th straight win since September, another Serb rubbed out the hot women's favourite and ended one of the longest streaks of her career.
In a result which throws the women's draw wide open, Ivanovic capitalised on Williams' poor movement to take her first ever sets against the world number one, winning 4-6, 6-3, 6-3.
Afterwards, Williams said she was on strong medication for a back injury which almost prompted her to pull out before her third-round win over Daniela Hantuchova.
"I made a tremendous amount of errors, shots I missed I normally don't miss, I haven't missed since the '80s. I'm just not used to missing those shots," she said.
"I think Ana just played a really good match. She did what it takes to win."
The upset robs Williams of the chance to join Chris Evert and Martina Navratilova on 18 Grand Slams, and draw nearer to Steffi Graf's Open-era record of 22.
Williams' coach, Patrick Mouratoglou, had said she was capable of winning all four Grand Slam titles this year -- a feat not achieved since Graf's sweep in 1988.
"Maybe I can win four in a row, but it seems like in the one year it's kind of difficult for me for whatever reason," said Williams, 32.
Her departure is a giant opportunity for those left in the draw, including Ivanovic, defending champion Victoria Azarenka and Li Na, who beat Ekaterina Makarova to reach the last eight.
Williams was on a 25-match winning streak, the second best of her career, after one of her most successful seasons in 2013 when she won a career-high 11 titles, including the French Open and US Open.
Ivanovic, the former world number one who is resurgent under new coach Nemanja Kontic, will now play Canada's Eugenie Bouchard, 19.
"I think all the struggles were just for moments like this," said the popular 26-year-old, who is striving to regain the highs of 2008 when she won the French Open and topped the world rankings.
Meanwhile, Djokovic had to endure a grating comedy act, but little threatening tennis, from Italian seed Fabio Fognini, a close friend whom he has known since junior days, to reach the quarter-finals.
The four-time champion kept focus to win 6-3, 6-0, 6-2 despite relentless antics at the other end from Fognini, who splashed water in his face, knocked a marshall's hat and clowned for the crowd.
"I knew that he's a flashy kind of player and that if he feels good, if he's focused enough, he can be very dangerous opponent on any surface," Djokovic said.
"So I did not take anything really for granted. I went out there preparing for this match as well as I do for any."
Spanish third seed David Ferrer doggedly ground down Germany's Florian Mayer 6-7 (5/7), 7-5, 6-2, 6-1 to set up a quarter-final with Tomas Berdych, who beat Kevin Anderson 6-2, 6-2, 6-3.
And China's Li was irresistible in her 6-2, 6-0 win over Russian 22nd seed Makarova as the two-time finalist reached the last eight in just under an hour.
The 2011 French Open winner will next play fellow veteran Flavia Pennetta, who at 31 is exactly one day older than the Chinese number one. Italy's Pennetta beat German Angelique Kerber 6-1, 4-6, 7-5.
"At least she's one day older than me, so I'll play an older player," quipped Li. "So nobody will talk about my age."
In the evening session, teenager Bouchard beat Australian wildcard Casey Dellacqua in three sets to become the first Canadian Grand Slam quarter-finalist in 22 years.
And Swiss number two Stanislas Wawrinka beat Tommy Robredo of Spain 6-3, 7-6 (7/3), 7-6 (7/5) to set up a clash with Djokovic, reprising last year's fourth-round classic which went to five gripping sets.