England prop Mako Vunipola has been ruled out of the rest of the Six Nations with an ankle injury.
The 28-year-old, one of England's best performers so far in the championship, suffered ankle ligament damage in Sunday's 44-8 win over France at Twickenham.
He is expected to be out for 10 weeks and will return to his club Saracens.
"It is obviously very disappointing to lose Mako at this stage," England head coach Eddie Jones said.
"He is an important player for us but it does provide an opportunity for the team to grow."
Vunipola missed the autumn Test matches with a calf injury, but returned to the international arena against Ireland, producing an astonishing individual performance in the 32-20 win.
He backed that up with a strong performance against France, before leaving the field at the start of the second half.
Vunipola's injury will present an opportunity to Exeter's Ben Moon and Leicester's Ellis Genge, who have both featured during the Six Nations.
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BBC Sport rugby union correspondent Chris Jones
With both Vunipolas and Manu Tuilagi running riot in the opening two rounds of the Six Nations, England had looked an infinitely more powerful and dynamic side to the one which struggled in 2018, so Mako's injury is a significant setback.
The prop was astonishingly good in England's ambush of Ireland in Dublin, and while Ben Moon and Ellis Genge have performed admirably when called upon, Moon can't match Vunipola's all-round game, while Genge is still raw.
With Leigh Halfpenny declared fit and Vunipola ruled out, Wales fans will feel a little more positive about their chances of halting the English juggernaut.