Joe Schmidt has included three uncapped players in a 42-man squad for the upcoming November internationals.
Leinster's Ross Byrne, Munster's Sam Arnold and Ulster's Will Addison are all included but Conor Murray has been left out as he continues to recover from a neck injury.
Ireland face Italy in Chicago on 3 November and then Argentina, New Zealand and the USA at the Aviva Stadium on successive Saturdays.
Schmidt said: "As always there have been a number of close calls in selection, meaning that some very good players have missed out in this particular window.
"The upcoming Guinness Series offers an exciting opportunity for the squad but will also be very challenging.
"We are certainly looking forward to getting back to a packed Aviva Stadium with the fantastic support that we get there."
Murray has not been selected as he awaits his first appearance of the season "within a few weeks".
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Despite missing out on another swing at the All Blacks, the scrum-half is looking forward to enjoying the games as a fan.
Speaking before the squad was named, he said: "This November is going to be really, really cool.
"The last few weeks at Munster and being a fan, it's been enjoyable to watch because the lads have gone quite well, particularly in Europe, but then there's the other side of being a player.
"I can see it going really well for Ireland and it will be tough to miss but...I'm getting myself properly fit, there's a lot of big things down the line that you can eye up.
"If you push this injury, get back early and take a bang again and not be fully ready it, you can derail that whole thing. So, I got to be realistic and take the time."
#IrishRugby— Irish Rugby (@IrishRugby) October 24, 2018
Here's the squad for the Guinness Series 2018 & @TheRugbyWeekend
?? v @Federugby - Nov 3rd https://t.co/d7TKO0j4J5
?? v @lospumas Nov 10 - Sold Out
?? v @AllBlacks Nov 17 - Sold Out
?? v @USARugby Nov 24 - https://t.co/fYpZbhQDUw#TeamOfUs #ShoulderToShoulder pic.twitter.com/fIIqFIPrI2
Out-half Byrne travelled to Australia for the summer series but was not capped.
England Under-20s graduate Addison has earned his first Ireland call-up, qualifying to represent Schmidt's men with his mother hailing from Fermanagh, while fellow centre Arnold has also impressed in the early season games.
Meanwhile, former Leinster player Ian McKinley has been included in the Italy squad to face Ireland in Chicago.
The out-half has three caps and is in line for an appearance against his native country after Conor O'Shea took the unusual step of naming his side ten days early.
#Italrugby, ecco gli Azzurri in campo a Chicago per la sfida con l’Irlanda il 3 novembre: https://t.co/xS7gCGQIil ??#IREvITA #insieme #rugbypassioneitaliana @TheRugbyWeekend pic.twitter.com/u6MRtdk0D5— Italrugby (@Federugby) October 24, 2018
IRELAND Squad 2018 Guinness Series & The Rugby Weekend:
Rory Best (Banbridge/Ulster) 111 (c)
Finlay Bealham (Buccaneers/Connacht) 7
Tadhg Beirne (Munster) 2
Jack Conan (Old Belvedere/Leinster) 9
Sean Cronin (St. Mary's College/Leinster) 62
Tadhg Furlong (Clontarf/Leinster) 26
Cian Healy (Clontarf/Leinster) 81
Iain Henderson (Ballynahinch/Ulster) 39
Rob Herring (Ballynahinch/Ulster) 6
Dave Kilcoyne (UL Bohemians/Munster) 22
Dan Leavy (UCD/Leinster) 10
Jack McGrath (St. Mary's College/Leinster) 50
Jordi Murphy (Ulster) 23
Sean O’Brien (UCD/Leinster) 51
Peter O'Mahony (Cork Constitution/Munster) 50 (vc)
Andrew Porter (UCD/Leinster) 8
Quinn Roux (Galwegians/Connacht) 6
Rhys Ruddock (St Mary’s College/Leinster) 19
James Ryan (UCD/Leinster) 11
John Ryan (Cork Constitution/Munster) 15
Niall Scannell (Dolphin/Munster) 9
CJ Stander (Shannon/Munster) 26
Devin Toner (Lansdowne/Leinster) 60
Josh van der Flier (UCD/Leinster) 10
Will Addison (Enniskillen/Ulster) *
Bundee Aki (Galwegians/Connacht) 9
Sam Arnold (Garryowen/Munster) *
Ross Byrne (UCD/Leinster) *
Joey Carbery (Munster) 12
Andrew Conway (Garryowen/Munster) 7
John Cooney (Terenure College/Ulster) 2
Keith Earls (Young Munster/Munster) 70
Robbie Henshaw (Buccaneers/Leinster) 36
Rob Kearney (UCD/Leinster) 86
Jordan Larmour (St. Mary's College/Leinster) 6
Kieran Marmion (Corinthians/Connacht) 22
Stuart McCloskey (Bangor/Ulster) 2
Luke McGrath (UCD/Leinster) 6
Garry Ringrose (UCD/Leinster) 14
Jonathan Sexton (St. Mary's College/Leinster) 76 (vc)
Jacob Stockdale (Ballynahinch/Ulster) 11
Darren Sweetnam (Cork Constitution/Munster) 2
* Denotes uncapped player