London - England's Mike Brown has been dropped for the first time in the Eddie Jones era after he was left out of the 25-man squad for Saturday's Test against South Africa.
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Brown had never been left out of Jones' first-choice matchday 23 when fit since the Australian took charge of England in 2015.
But the Harlequins fullback, who has 72 caps, will play no part against South Africa despite impressing on the wing when England faced the Springboks in three Tests earlier this year.
Brown's tenacity and strength have made him a key figure for successive England coaches.
He has scored 13 tries since making his England debut in 2007, but his exclusion now casts doubt over his involvement in next year's World Cup.
With the 33-year-old out of contention, Elliot Daly is certain to continue at fullback.
Jones will choose two wings from Chris Ashton, Jonny May and Jack Nowell.
If Ashton is picked, he will be making his first international appearance since 2014.
Number eight Ben Morgan has also been released, leaving Bath's Zach Mercer in position to make his England debut against the Springboks.
Northampton's Courtney Lawes has been ruled out with a back injury and will remain in Portugal for rehabilitation when England fly home from their training camp.
Forwards coach Steve Borthwick said England were hopeful Lawes would be available for next weekend's Test against New Zealand.
"He's feeling positive. He's done plenty of work already this morning (Tuesday) and is progressing well," Borthwick said.
South African-born pair Michael Rhodes and Nick Schonert were also released.
England's 25-man squad:
Tom Curry (Sale Sharks), Charlie Ewels (Bath Rugby), Jamie George (Saracens), Dylan Hartley (Northampton Saints) co-captain, Alec Hepburn (Exeter Chiefs), Maro Itoje (Saracens), George Kruis (Saracens), Zach Mercer (Bath Rugby), Ben Moon (Exeter Chiefs), Brad Shields (Wasps), Kyle Sinckler (Harlequins), Elliott Stooke (Bath Rugby), Harry Williams (Exeter Chiefs), Mark Wilson (Newcastle Falcons)
Chris Ashton (Sale Sharks), Danny Care (Harlequins), Elliot Daly (Wasps), Owen Farrell (Saracens) co-captain, George Ford (Leicester Tigers), Jonny May (Leicester Tigers), Jack Nowell (Exeter Chiefs), Henry Slade (Exeter Chiefs), Ben Te’o (Worcester Warriors), Manu Tuilagi (Leicester Tigers), Ben Youngs (Leicester Tigers)