England star Lewis Moody will miss this season's entire RBS 6 Nations Championship after suffering a broken ankle.
Moody, who was injured yesterday, has undergone surgery and faces up to three months on the sidelines.
It is the latest setback in the 30-year-old Leicester flanker's injury-hit career, and means he is now battling to regain full fitness in time to make a selection case for the British and Irish Lions tour of South Africa later this year.
A decision on Moody's replacement in the England elite player squad will be made following this weekend's final round of Heineken Cup and European Challenge Cup pool games.
The squad heads to Portugal for warm weather training on Sunday, with Bath captain Michael Lipman and London Irish prospect Steffon Armitage heading the list of candidates available to England manager Martin Johnson.
Moody's absence is yet another blow for Johnson, who will be without Wasps flanker Tom Rees at least for the first three RBS 6 Nations games, while second-row forward Tom Palmer will miss the whole tournament due to shoulder trouble.
Bath prop Matt Stevens was removed from the England squad earlier this week following his confession that he had failed a drugs test. Stevens is currently suspended from all rugby.
Moody, a member of England's last two World Cup campaigns with more than 50 caps, only returned to action last October after suffering an Achilles injury during the opening game of last season's RBS 6 Nations tournament against Wales. He also had a hip problem.
Moody said: "There is never a good time to get injured, but it is even more frustrating when you are playing well.
"I have felt good since I got back into the (Leicester) team, and I was gutted when I found out the details and a break was confirmed."
Moody would have been a key part of Tigers' plan in their crunch Heineken Cup clash against the Ospreys tomorrow, and Leicester forwards coach Richard Cockerill admitted: "It is a big blow.
"Lewis has been in excellent form for us since his return to the team a couple of months ago, and he is an experienced player at the top level.
"We feel for him - he has been unlucky - but we have a strong squad at Leicester, and whoever comes in will now have their opportunity."
Johnson added: "I know how hard Lewis worked to recover from his previous injury, so my thoughts are with him and I wish him a speedy return to fitness."
The RBS 6 Nations Championship 2015 was not poised to go down as one of the more "vintage" Championships, though there was great anticipation as the action headed into its final day. What transpired was something that nobody could foresee: "The Greatest Day in Rugby's Greatest Championship."