Paris: Nine-time champion Rafael Nadal sensationally quit the French Open with a left wrist injury on Friday as Andy Murray cruised into the last-16.
Nadal, 29, stunned Roland Garros by calling a news conference at just 10 minutes notice to announce he was pulling out.
The Spaniard said he had been playing with an anesthetic injection in the wrist in the first two rounds and that MRI scans had shown that the injury was getting worse.
"It`s not broken, but if I continue to play it will be 100 percent broken in a few days," said an emotional Nadal, the fourth seeded winner of 14 majors.
"To win the tournament I need five more matches, and the doctor says that`s 100% impossible."
Nadal, plagued by knee and wrist injuries througout his career, added: "This is a very bad position, but that`s life.
"It`s obvious that if it`s not Roland Garros I would not take risks on playing the first two days, but it is the most important event of the year for me so we tried our best."
Despite his latest setback, the charismatic Spaniard said he will keep playing although his participation at Wimbledon next month is now in serious doubt.
"This is a tough moment and the toughest press conference I have ever had to give but it`s not the end," said Nadal, who won the first of his nine French Opens as a 19-year-old in 2005.
Nadal`s withdrawal gives compatriot Marcel Granollers a walkover into the last 16.
It`s also a huge boost to world number one Novak Djokovic`s hopes of lifting a first French Open crown.
Nadal and Djokovic were seeded to meet in the semi-finals next Friday -- the date of the Spaniard`s 30th birthday.
Second seed Murray cut down Croatian giant Ivo Karlovic to reach the last-16.
Murray, a three-time semi-finalist, had needed two five-set matches and three days of play to get to the last 32.
But on Friday the 29-year-old needed just a shade under two hours to beat 6ft 11in (2.11m) Karlovic 6-1, 6-4, 7-6 (7/3).
It was his seventh win in seven matches against the 37-year-old as Murray goes on to face either John Isner of the United States or Teymuraz Gabashvili of Russia.
"At the end it was very close. I got off to a quick start and against someone like Ivo that`s very important," said Murray.
Kei Nishikori of Japan also reached the last 16 with a 6-3, 6-4, 3-6, 2-6, 6-4 win over Spain`s Fernando Verdasco.
The fifth seed, a quarter-finalist in 2015, will play Richard Gasquet for a place in the quarter-finals after the Frenchman defeated Australian Nick Kyrgios 6-2, 7-6 (9/7), 6-2.
Canada`s eighth seed Milos Raonic overcame a left hip injury to defeat Slovakian lucky loser Andrej Martin, the world number 133.
Raonic won 7-6 (7/4), 6-2, 6-3 but only after requiring a medical timeout at the start of the third set to treat a hip injury.
Raonic, a quarter-finalist in 2014, next faces 55th-ranked Albert Ramos-Vinolas after the Spaniard stunned American 23rd seed Jack Sock 6-7 (2/7), 6-4, 6-4, 4-6, 6-4.
Ramos-Vinolas, 28, had not won a match at Roland Garros since 2011 before this year.
Spanish fourth seed and last year`s Wimbledon runner-up Garbine Muguruza won the last nine games to knock out Belgium`s Yanina Wickmayer 6-3, 6-0.
Muguruza, a quarter-finalist in the last two years, next faces dangerous 2009 champion Svetlana Kuznetsova who beat Russian Fed Cup teammate Anastasia Pavlychenkova 6-1, 6-4.
Romanian sixth seed Simona Halep, the runner-up to Maria Sharapova in 2014, needed three sets to see off 18-year-old Japanese player Naomi Osaka 4-6, 6-2, 6-3.
Halep, 24, next faces 2010 finalist Sam Stosur who defeated 2015 runner-up Lucie Safarova of the Czech Republic 6-3, 6-7 (0/7), 7-5.
Czech 10th seed Petra Kvitova became the fourth top 10 seed to exit by the third round after she lost 6-0, 6-7 (3/7), 6-0 to American world number 108 Shelby Rogers.
Kvitova, a semi-finalist in 2012, committed 36 unforced errors as 23-year-old Rogers reached the last 16 of a Grand Slam for the first time.
Third seed Angelique Kerber, fifth-seeded Victoria Azarenka and Roberta Vinci, the seventh seed, all flopped in the first round.
Rogers, who had put out Czech 17th seed Karolina Pliskova in the first round, next plays Romanian 25th seed Irina-Camelia Begu.
With Halep also through, it`s the first time since 1997 that two Romanian women have made the last-16.
Later Friday, defending champion and third seed Stan Wawrinka takes on Frenchman Jeremy Chardy.