Eddie Jones has named his initial 33-man England squad for the Six Nations and given seven players their first senior international call-ups.
Josh Beaumont, Jack Clifford, Elliot Daly, Ollie Devoto, Sam Hill, Paul Hill and Maro Itoje are the new faces chosen in Jones's first squad since taking over.
Meanwhile, Chris Ashton, Dylan Hartley and Marland Yarde, who missed selection for England's Rugby World Cup squad last year, return to the fold.
"The long-term strategy for England is to develop a side who can be the most dominant team in world rugby, so we have chosen a lot of new players on the growth we see in them," Jones told England Rugby's website.
"We see these players growing into England players of the future and developing into a side who can be the best in the world. Our aim is to develop a squad where there is depth and competition in every position."
Among those to have been left out are Tom Youngs, Brad Barritt, Tom Wood, Geoff Parling and Danny Cipriani.
Jones added: "I have spoken to some of the players who have not been selected. Naturally they will be disappointed and that is how it should be.
"They know what they need to do to get back into this squad. The door is not shut for anyone. There is no such thing as a shut door because of injuries and loss of form. There will always be opportunities to anyone playing consistently well in the Premiership and Europe."
It is not yet known who England's captain will be under Jones, with both current skipper Chris Robshaw and the man expected to take over, hooker Hartley, in the squad.
England's first Six Nations contest is away to Scotland at Murrayfield on February 6.
England squad for 2016 Six Nations
Forwards
Josh Beaumont (Sale Sharks)
Dan Cole (Leicester Tigers)
Luke Cowan-Dickie (Exeter Chiefs)
Jack Clifford (Harlequins)
Jamie George (Saracens)
Dylan Hartley (Northampton Saints)
James Haskell (Wasps)
Paul Hill (Northampton Saints)
Maro Itoje (Saracens)
George Kruis (Saracens)
Matt Kvesic (Gloucester Rugby) *injury replacement for Dave Ewers (Exeter Chiefs)
Joe Launchbury (Wasps)
Courtney Lawes (Northampton Saints)
Joe Marler (Harlequins)
Matt Mullan (Wasps)
Chris Robshaw (Harlequins)
Henry Thomas (Bath Rugby) *injury replacement for Kieran Brookes (Northampton Saints)
Billy Vunipola (Saracens)
Mako Vunipola (Saracens)
Backs
Chris Ashton (Saracens)
Mike Brown (Harlequins)
Danny Care (Harlequins)
Elliot Daly (Wasps)
Ollie Devoto (Bath Rugby) *injury replacement for Manu Tuilagi (Leicester Tigers)
Owen Farrell (Saracens)
George Ford (Bath Rugby)
Alex Goode (Saracens)
Sam Hill (Exeter Chiefs) *injury replacement for Henry Slade (Exeter Chiefs)
Jonathan Joseph (Bath Rugby)
Jack Nowell (Exeter Chiefs)
Anthony Watson (Bath Rugby)
Marland Yarde (Harlequins)
Ben Youngs (Leicester Tigers)