George Ford has been ruled out of England's summer tour to Japan and New Zealand because of an Achilles injury.
Ford started at fly-half throughout this year's Six Nations but, having completed the club season with Sale, it has been decided he needs time to recover from the pre-existing condition.
"Naturally we're disappointed that George won't be with us in Japan and New Zealand," England head coach Steve Borthwick said.
"Following specialist medical advice, and in consultation with George himself, we have decided this is the best course of action.
"George is a big part of the England team and is an excellent professional who I know will rehab diligently to ensure he gets himself right as soon as he can."
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Ford, who missed seven months of the 2022-23 season with an Achilles injury, was part of England's training camp last week but Borthwick must now plan to take on the Brave Blossoms and All Blacks without two of his World Cup fly-halves following Owen Farrell's decision to join Racing 92.
It leaves Northampton's Premiership-winning ringmaster Fin Smith and Marcus Smith of Harlequins in a shootout for the No 10 jersey, with rookie Charlie Atkinson most likely to tour as the third playmaker.
Fin Smith started the Six Nations on the bench in support of Ford before losing his place to his namesake once the British and Irish Lion had recovered from injury.
But the 22-year-old Saint has produced an impressive club season as evidenced by claiming the Rugby Players Association's player of the year award and a Premiership winners medal and will see this as the chance to challenge the pecking order.