Paris - Defending champion and world No 1 Serena Williams was knocked out of the French Open on Wednesday by Spain's Garbine Muguruza as the women's tournament was thrown wide open.
The top seed lost 6-2, 6-2 in the second round to the world number 35 with her defeat coming just an hour after sister Venus also went out 2-6, 6-3, 6-4 to Slovak teenager Anna Schmiedlova.
It was the earliest exit for a defending champion at Roland Garros since 2005 when Anastasia Myskina of Russia went out in the first round.
Wednesday's defeat was Serena's worst at a Grand Slam in terms of games won and was only the second time in her career she had been beaten at a major in the round of 64.
The last time that happened was on her debut at the 1998 Australian Open.
It was also just the fourth time the Williams sisters had lost on the same day at a major.
"Nothing worked today," said 17-time major winner Serena who hit just eight winners and a huge 29 unforced errors with five double faults.
"I just couldn't serve. But you can't be on form every day. I hate to be off at a Grand Slam but it happens, it's not the end of the world.
"I will have to work five times as hard to make sure it doesn't happen again," added the 32-year-old American who suffered her only Grand Slam first round loss in Paris in 2012.
Muguruza immediately won praise for her performance.
"Shocker at the French - Serena loses to Garbine Muguruza. Garbine is here to stay, that's for sure, quite a talent," tweeted Martina Navratilova.
The young Spaniard was over-joyed by her performance.
"Today's a great day," she said.
Serena'a defeat was good news for Maria Sharapova who is now the overwhelming title favourite with second seed Li Na having been knocked out in the first round on Tuesday.
The Williams sisters had been scheduled to meet in the third round.
Instead the tournament will get Muguruza against Schmiedlova, the 19-year-old Slovak who ended 32-year-old Venus's 17th French Open with a 2-6, 6-3, 6-4 win.
Schmiedlova was just a month old when the American made her professional debut back in 1994.
"It's the biggest win of my career," said world number 56 Schmiedlova who had lost to Venus in straight sets in Miami this season.
"I have big respect for her. She's a great player and I still cannot believe I won."
Defeat for Venus, the 29th seed, meant she has now failed to get beyond the second round in Paris on her last three visits.
She was undone by 47 unforced errors on a half-full Philippe Chatrier court and despite saving two match points it was all too much for mother Oracene who was caught on TV napping as Venus slipped to defeat.
"I think she's very good already, and she's going to be even better as she continues to play. I see wonderful things for her," said Venus of her opponent.
Later Wednesday, second seed Novak Djokovic, the 2012 runner-up who needs a French Open title to complete a career Grand Slam, faces Jeremy Chardy of France for a place in the last 32.
Djokovic holds an 8-0 career lead over the world number 42 with his stranglehold illustrated by never surrendering a single set to Chardy.
However, the Frenchman came into Roland Garros with a win over Roger Federer in Rome under his belt.
Federer, the fourth seed, looks to claim his 60th win at the tournament when he takes on 21-year-old Argentine qualifier Diego Sebastian Schwartzman.
Maria Sharapova, the seventh seeded 2012 champion, faces Bulgaria's Tsvetana Pironkova, a Wimbledon semi-finalist in 2010.
Latvian 18th seed Ernests Gulbis eased past Argentine qualifier Facundo Bagnis 6-2, 7-5, 6-0 and will next face Czech veteran Radek Stepanek who knocked out Russian 15th seed Mikhail Youzhny 6-0, 6-3, 3-6, 6-4.
In a first round match held over from Tuesday night, American Steve Johnson completed a 4-6, 6-7 (7/9), 7-6 (7/3), 6-3, 6-3 comeback win over French world number 406 Laurent Lokoli.
The teenage Frenchman had two match points in the third set.
Italian women's 12th seed Flavia Pennetta was knocked out by Sweden's Johanna Larsson who now faces 18th seed Eugenie Bouchard.
The highly-rated 20-year-old Canadian, who made the Australian Open semi-finals this year and captured her first title in Nuremberg at the weekend, put out Germany's Julia Goerges 2-6, 6-2, 6-1.
Results on Wednesday at the French Open, the fourth day of the season's second Grand Slam tournament at Roland Garros (x denotes seeded player):
Tomas Berdych (CZE x6) bt Aleksandr Nedovyesov (KAZ) 6-7 (4/7), 6-4, 7-5, 6-3
Roberto Bautista Agut (ESP x27) bt Benot Paire (FRA) 6-4, 7-6 (7/4), 6-2
Tommy Robredo (ESP x17) bt Kenny De Schepper (FRA) 6-2, 6-3, 6-3
Radek Stepanek (CZE) bt Mikhail Youzhny (RUS x15) 6-0, 6-3, 3-6, 6-4
Ernests Gulbis (LAT x18) bt Facundo Bagnis (ARG) 6-2, 7-5, 6-0
Dmitry Tursunov (RUS x31) bt Sam Querrey (USA) 6-4, 7-5, 6-1
Roger Federer (SUI x4) bt Diego Schwartzman (ARG) 6-3, 6-4, 6-4
Milos Raonic (CAN x8) bt Jir Vesel (CZE) 7-6 (7/4), 6-4, 6-1
Gilles Simon (FRA x29) bt Alejandro Gonzlez (COL) 6-4, 6-0, 6-2
Marcel Granollers (ESP) bt Aleksandr Dolgopolov (UKR x20) 1-6, 3-6, 6-3, 6-0, 6-2
Martin Klizan (SVK) bt Robin Haase (NED) 6-1, 3-6, 6-1, 1-6, 7-5
Jo-Wilfried Tsonga (FRA x13) bt Jurgen Melzer (AUT) 6-2, 6-3, 6-4
Jerzy Janowicz (POL x22) bt Jarkko Nieminen (FIN) 7-6 (7/4), 7-6 (7/4), 6-4
Marin Cilic (CRO x25) bt Tobias Kamke (GER) 6-3, 3-6, 6-3, 6-0
Novak Djokovic (SRB x2) bt Jrmy Chardy (FRA) 6-1, 6-4, 6-2
Steve Johnson (USA) bt Laurent Lokoli (FRA) 4-6, 6-7 (7/9), 7-6 (7/3), 6-3, 6-3
Garbie Muguruza (ESP) bt Serena Williams (USA x1) 6-2, 6-2
Anna Schmiedlov (SVK) bt Venus Williams (USA x29) 2-6, 6-3, 6-4
Dominika Cibulkova (SVK x9) bt Tamira Paszek (AUT) 6-3, 6-4
Carla Surez (ESP x14) bt Timea Bacsinszky (SUI) 7-5, 1-6, 6-4
Johanna Larsson (SWE) bt Flavia Pennetta (ITA x12) 5-7, 6-4, 6-2
Eugnie Bouchard (CAN x18) bt Julia Grges (GER) 2-6, 6-2, 6-1
Daniela Hantuchova (SVK) bt Claire Feuerstein (FRA) 6-1, 6-4
Angelique Kerber (GER x8) bt Varvara Lepchenko (USA) 6-2, 7-5