England captain Rio Ferdinand will miss the World Cup after suffering ligament damage to his left knee in the team's first training session in South Africa.
The 31-year-old has been ruled out for up to six weeks and Tottenham centre-back Michael Dawson is to fly out later on Friday as his replacement.
Steven Gerrard will now take over as England captain for the tournament.
"Everyone with the squad is very disappointed and sorry for Rio," said England manager Fabio Capello.
"It was an accidental injury in training, but had nothing to do with the pitch."
Ferdinand was sent to the Fearncrest Hospital in Rustenburg for a scan after suffering the injury late on in training in a challenge with striker Emile Heskey, described by Capello as "a normal tackle".
The Manchester United defender was later seen emerging from the hospital on crutches, and a second medical opinion confirmed that he had no chance of featuring in South Africa.
His withdrawal from what would have been his fourth World Cup is a devastating end to an already disappointing season for Ferdinand, who, because of a back injury, had been restricted to only 13 Premier League starts for United and 21 appearances overall.
The centre-back had appeared to have overcome his injury problems when he trained with no setbacks at England's two-week World Cup training camp in Austria. He also came through the recent friendly victories over Mexico and Japan.
Dawson was the only centre-back dropped by Capello when he trimmed his 30-man training squad to the 23 for the tournament.
The 26-year-old enjoyed a fine season as Spurs finished in fourth place in the Premier League, but is uncapped at international level.
"It's a crazy game and things can change in a split second," said Dawson.
"One minute I'm trying to arrange my holiday, then I get a call asking if I was on holiday because Rio had pulled out of training.
Dawson has yet to win a senior cap
"I said 'no' and then I was just waiting by the phone before getting a call saying I would be picked up in an hour.
"I'll be going out there still having not yet won a senior cap, so where better place to get one if that was to happen."
He also told Tottenham's website: "For Rio to get injured, there would be no worse feeling for him as a player. To miss the biggest tournament in the world as the captain, I feel for him. "
Dawson's Spurs manager Harry Redknapp had suggested Capello only picked the defender in his 30-man party to "make up the numbers". But the England coach said: "I didn't hear when Redknapp said that. For me, all 30 players who stayed with me in Austria are important, really important for me.
"For me, it was important to find out and learn about all the players as they trained together. It's not important what other managers think about the players I've chosen. Dawson will be pleased to come here."
Dawson will be joining Spurs team-mates Peter Crouch, Jermain Defoe, Aaron Lennon and Ledley King at the England camp.
Capello must now decide whether Dawson, King, Jamie Carragher or Matthew Upson should replace Ferdinand alongside John Terry at the heart of England's defence.
The Italian made Ferdinand captain of England in February, having stripped Terry of the role following allegations that the Chelsea defender had an affair with the ex-girlfriend of former team-mate Wayne Bridge.
Ferdinand, who made his England debut back in 1997 as a 19-year-old, has 78 caps and has scored three goals for his country.
Shearer - 'Let's win it for Rio'
Friday had started on a more positive note for England, with the news that midfielder Gareth Barry - who had been a major doubt after suffering an ankle injury towards the end of Manchester City's season - trained with the squad.
"Gareth Barry is improving every day," said Capello.
"In the afternoon he is training in the gym with the physio and in the morning always with the team.
"He is not completely training with the team as we have to be very careful."
Meanwhile, goalkeeper David James sat out the training session after suffering a slight knee problem.
His injury is not thought to be too severe and is related to the 11-hour overnight flight from London to South Africa on Thursday.
England's World Cup campaign begins with their game against the United States in Rustenburg on 12 June.
This page is best viewed in an up-to-date web browser with style sheets (CSS) enabled. While you will be able to view the content of this page in your current browser, you will not be able to get the full visual experience. Please consider upgrading your browser software or enabling style sheets (CSS) if you are able to do so.