Gloucester's Mike Tindall will miss England's tour to South Africa after breaking his right leg in Friday's Premiership loss to Newcastle.
Tindall played in four of this year's Six Nations games
Tindall faces 12 weeks on the sidelines but should be fit to return ahead of England's defence of the World Cup.
He will also definitely miss the end of season Premiership play-offs.
Newcastle's Jonny Wilkinson is also a doubt for England's tour after damaging ribs in the same game, with a "short period" on the sidelines forecast.
"Jonny has damaged rib cartilage - he did it last week and aggravated it again," said Falcons director of rugby John Fletcher.
"He'll be out for a short period of time but we can't say how long until the doctors have had a look at it."
England play the Springboks in Bloemfontein on 26 May, and again on 2 June in Pretoria.
Brian Ashton's squad is already likely to be severely depleted with the likelihood of either Wasps or Leicester, or both, being involved in the Heineken Cup final on 20 May, five days after England leave for South Africa.
"I am desperately disappointed for Mike and I hope he makes a full and speedy recovery," Ashton said on Saturday.
I feel desperately sorry for Mike
Tindall had a pin inserted in his lower right leg on Saturday, having come off worse in a a colllision with England midfielder Toby Flood early in the second half at Kingston Park on Friday.
"I stepped one way and I think Mike instinctively stepped the other, then I felt his shin hit my thigh really hard," recalled Flood.
"It was just one of those things nobody can do anything about, but I feel desperately sorry for Mike because he is a nice bloke and a great player.
"It is deeply upsetting to see anybody seriously injured, and I just wish him all the best."
Tindall, a World Cup winner in 2003, started four Six Nations matches this season and is a key part of Ashton's World Cup planning, as well as a central cog in Gloucester's title bid.
Director of rugby Dean Ryan said: "Losing Mike is a very serious blow for us but we wish him all the best and we are right behind him."
Wilkinson, according to Flood, should be able to recover fairly quickly though.
"He just took a whack in the ribs and he was fine down in the changing room after the match," he added.
"Obviously, he is a bit sore, but it doesn't seem too serious, thankfully."