Billy Vunipola and Jonny are the high-profile omissions from Steve Borthwick's England squad for the upcoming Six Nations.
Having been named as Eddie Jones's replacement at the end of last year, Borthwick is hoping to spearhead an upturn in fortunes after a disappointing 2022.
As expected, Borthwick has moved to make his mark in terms of selection, including as many as five uncapped players in a group of 36.
Fin Smith, Ollie Hassell-Collins, George McGuigan, Cadan Murley and Jack Walker are all in line to earn their first opportunities on the international scene.
However, Vunipola and May, who both started England's 27-13 defeat to South Africa in their last game on November 26, have been left out.
Despite the absence of the 64 and 72-capped duo, Borthwick has talked up the make-up of his first squad, hoping that they can restore some pride after the frequent poor performances over the past 12 months.
Borthwick said: "This is an exciting squad, with a blend of Six Nations experience and young talent, and includes players who are in excellent form in the Premiership.
"I know the players can't wait to get back to Twickenham and give our fans a performance they can be proud of. The hard work for the Scotland game starts now."
England start their campaign almost a year to the day since they succumbed 20-17 to Scotland at Murrayfield at the start of the 2022 Six Nations.
Although England were able to finish in third position in the table, they lost three of their five matches, before ending the year with just one win from their four Autumn internationals.
Squad in full
Forwards: Ollie Chessum, Dan Cole, Ben Curry, Alex Dombrandt, Ben Earl, Ellis Genge, Jamie George, Joe Heyes, Jonny Hill, Nick Isiekwe, Maro Itoje, Courtney Lawes, Lewis Ludlam, George McGuigan, Bevan Rodd, Sam Simmonds, Kyle Sinckler, Mako Vunipola, Jack Walker, Jack Willis
Backs: Elliot Daly, Owen Farrell, Tommy Freeman, Ollie Hassell-Collins, Dan Kelly, Max Malins, Joe Marchant, Alex Mitchell, Cadan Murley, Henry Slade, Fin Smith, Marcus Smith, Freddie Steward, Manu Tuilagi, Jack van Poortvliet, Ben Youngs