Ben Youngs, England's most-capped men's player, has been dropped by England for Sunday's Six Nations clash with Italy.
The Leicester scrum-half, with 122 caps to his name, makes way for Northampton rival Alex Mitchell in Steve Borthwick's 29-man squad.
Also out are Ben Curry, who made his Six Nations debut against Scotland - suggesting Jack Willis will get the start this weekend.
Anthony Watson, who came off the bench in the Calcutta Cup, is another to make way - replaced by fit-again Henry Arundell.
England take on Italy at Twickenham on Sunday knowing a win is a necessity ahead of trips to Wales and Ireland, with the home clash with France also on the horizon.
Speaking after the disappointing defeat to Scotland, Borthwick admitted he knew he had a big task on his hands when replacing Eddie Jones.
"When I looked at the team in the autumn, when I measured the team and got all the data for the team, we weren't good at anything. It was as frank as that," he said.
"So we are trying to build some strengths in this team and some bits we are pleased about and some bits we are disappointed about. My job is to make sure we get some improvements for Italy."
Full squad
Forwards
Ollie Chessum (Leicester Tigers, 6 caps)
Dan Cole (Leicester Tigers, 96 caps)
Alex Dombrandt (Harlequins, 10 caps)
Tom Dunn (Bath Rugby, 3 caps)
Ben Earl (Saracens, 14 caps)
Ellis Genge (Bristol Bears, 44 caps)
Jamie George (Saracens, 73 caps)
Nick Isiekwe (Saracens, 9 caps)
Maro Itoje (Saracens, 63 caps)
Lewis Ludlam (Northampton Saints, 15 caps)
David Ribbans (Northampton Saints, 3 caps)
Kyle Sinckler (Bristol Bears, 57 caps)
Mako Vunipola (Saracens, 75 caps)
Jack Walker (Harlequins, uncapped)
Jack Willis (Toulouse, 6 caps)
Backs
Henry Arundell (London Irish, 3 caps)
Owen Farrell (Saracens, 102 caps)
Tommy Freeman (Northampton Saints, 3 caps)
Ollie Hassell-Collins (London Irish, 1 cap)
Ollie Lawrence (Bath Rugby, 8 caps)
Max Malins (Saracens, 15 caps)
Joe Marchant (Harlequins, 14 caps)
Alex Mitchell (Northampton Saints, 1 cap)
Henry Slade (Exeter Chiefs, 52 caps)
Fin Smith (Northampton Saints, uncapped)
Marcus Smith (Harlequins, 18 caps)
Freddie Steward (Leicester Tigers, 18 caps)
Manu Tuilagi (Sale Sharks, 50 caps)
Jack van Poortvliet (Leicester Tigers, 8 caps)