Captain Rory Best and Johnny Sexton are among several Ireland players who have been rested for the first November Test against Italy in Chicago on Saturday.
Joe Schmidt has also omitted Peter O'Mahony, Rob Kearney and Keith Earls from the squad for the clash with former Ireland international Conor O'Shea's side at Soldier Field.
Uncapped duo Ross Byrne and Will Addison are among the 26 players who will cross the Atlantic.
Byrne will compete with Joey Carbery to start at fly-half as Sexton gets a breather, while versatile utility back Addison will be hoping to win his first cap.
John Cooney and Luke McGrath are the scrum-half options, with Kieran Marmion staying at home.
Forwards: Finlay Bealham,, Tadhg Beirne, Jack Conan, Sean Cronin, Tadhg Furlong, Dave Kilcoyne, Jack McGrath, Jordi Murphy, Andrew Porter, Quinn Roux, Rhys Ruddock, James Ryan, Niall Scannell, Devin Toner, Josh van der Flier.
Backs: Will Addison, Bundee Aki, Ross Byrne, Joey Carbery, Andrew Conway, John Cooney, Jordan Larmour, Luke McGrath, Garry Ringrose, Jacob Stockdale, Darren Sweetnam.