Ireland coach Eddie O'Sullivan will hand youngsters Tommy Bowe and Denis Leamy their international debuts against the USA on Saturday, while resting Ronan O'Gara - the 17-point hero of their landmark win over South Africa.
OSullivan, a former national technical director with the Eagles, has made eight changes and two positional switches from the side which defeated the Springboks 17-12 three days ago.
Winger Bowe, 20, and flanker Leamy, 22, who replaces Wasps openside Johnny OConnor, are the only uncapped players in a side skippered once more by Brian ODriscoll on his 54th appearance.
ODriscoll is the only player remaining in his usual position in the backs, with Leicesters Geordan Murphy reverting to full-back and Shane Horgan manning the right wing.
Ulster veteran David Humphreys will make his first international start since kicking 18 points in a 45-17 Rugby World Cup pool win over Romania last October.
Humphreys is nine points short of the 500-point mark.
Kevin Maggs, Donncha OCallaghan, Guy Easterby, Frankie Sheahan and Marcus Horan return to the fold - with the latter three having made their debuts against the Americans in June 2000.
OSullivan has broken up the OGara-Peter Stringer partnership for the first time in 13 games, with the Munster duo benched, alongside captain Anthony Foley and Leinster pairing Shane Byrne and Girvan Dempsey.
Lock Malcolm OKelly - two caps short of equalling Mike Gibsons record haul of 69 - sits the game out.
Ireland: G Murphy (Leicester); S Horgan (Leinster), B ODriscoll (Leinster, capt), K Maggs (Ulster), T Bowe (Ulster); D Humphreys (Ulster), G Easterby (Leinster); M Horan (Munster), F Sheahan (Munster), J Hayes (Munster), D OCallaghan (Munster), P OConnell (Munster), S Easterby (Llanelli Scarlets), D Leamy (Munster), E Miller (Leinster).
Replacements: S Byrne (Leinster), S Best (Ulster), L Cullen (Leinster), A Foley (Munster), P Stringer (Munster), R OGara (Munster), G Dempsey (Leinster).