Leinster's inexperienced fly-half Joey Carbery could make his Test debut when Ireland attempt to stop New Zealand extending their record match-winning streak in Chicago on Saturday.
Auckland-born Carbery has just nine senior Leinster appearances to his name and turns 21 on November 1, but could now take a seat on Ireland's bench for the autumn Test opener against the double world champions.
Ulster's Paddy Jackson will miss the USA trip due to personal reasons, leaving Carbery the most likely understudy to Johnny Sexton.
Ireland must also bid to deny New Zealand a 19th consecutive victory without influential forwards Sean O'Brien, Iain Henderson and Peter O'Mahony.
"Players returning to full fitness Sean O'Brien, Iain Henderson and Peter O'Mahony along with Paddy Jackson, unavailable due to personal reasons, will not make the trip to Chicago," the Irish Rugby Football Union (IRFU) confirmed in a statement.
Sexton should start Saturday's Soldier Field clash, with Leinster team-mate Carbery now likely to take a seat on the bench in Ulster playmaker Jackson's absence.
Carbery, who has been in fine form in the Guinness PRO12, has been promoted to Ireland's senior squad after winning nine U20 caps for the autumn series ahead of Ian Madigan, now plying his trade in Bordeaux.
Leinster flanker O'Brien has only just returned from long-term hamstring trouble, and has been deemed not quite ready for Test rugby.
Ireland will hope the combative loose-forward will be available for selection by the time they face New Zealand again, in Dublin on November 19.
O'Mahony has recently beaten the knee ligament problem that ended his World Cup 2015 campaign prematurely in the 24-9 pool stage victory over France.
As with O'Brien, Ireland are taking few risks with the Munster captain in the hope the 27-year-old will be fully fit for the second clash with the All Blacks.
Powerful back-five forward Henderson suffered a shoulder injury in Ulster's 19-18 Champions Cup victory over Exeter Chiefs on October 22.
Ireland remain hopeful the 24-year-old can make a quick recovery to play a meaningful part in what will be another gruelling November series.
Ireland's 27-man squad: F Bealham (Connacht), R Best (capt) (Ulster), J Carbery, S Cronin (both Leinster), U Dillane (Connacht), T Furlong (Leinster), C Gilroy (Ulster) C Healy, J Heaslip, R Henshaw (all Leinster), B Holland (Munster), R Kearney (Leinster), K Marmion (Connacht), J McGrath, L McGrath, J Murphy (all Leinster), C Murray (Munster), J Payne (Ulster), G Ringrose (Leinster), D Ryan, J Ryan (both Munster), J Sexton (Leinster), CJ Stander (Munster), D Toner (Leinster), A Trimble (Ulster), J Van der Flier (Leinster), S Zebo (Munster).