Injured scrum-half Jamison Gibson-Park will miss Ireland's two-Test series against world champions South Africa next month, with Jack Conan also absent from the squad announced on Tuesday.
First-choice number nine Gibson-Park is ruled out by a hamstring injury, while Leinster team-mate Conan is unavailable for personal reasons.
Ireland coach Andy Farrell has handed a first senior call-up to Ulster lock Cormac Izuchukwu and included uncapped Leinster pair Jamie Osborne and Sam Prendergast in a 35-man squad captained by Peter O'Mahony.
The Six Nations winners face world champions the Springboks in Pretoria on July 6 and again a week later in Durban.
Full-back Hugo Keenan is absent after he was named in Ireland's rugby sevens squad for the Paris Olympics but Jimmy O'Brien returns from injury.
Hooker Rob Herring is also back but Connacht wing Mack Hansen remains sidelined, while Ulster lock Iain Henderson is out after undergoing toe surgery.
Connacht scrum-half Caolin Blade, who has two international caps, benefits from the absence of the influential Gibson-Park.
Ireland have won the last three meetings between the nations, including a 13-8 success during the pool stage at last year's World Cup in France.
But the Springboks went on to retain the Webb Ellis Cup by beating New Zealand, who eliminated the Irish at the quarter-final stage, in the final.
"Travelling to South Africa to play a Test series against the defending world champions provides no greater test for us, and it is another valuable opportunity for us to further grow and develop from the Guinness Six Nations," said head coach Farrell.
"The group understands the need to hit the ground running, ensuring we are the best version of ourselves for the challenge ahead."
Ireland squad for South Africa tour
Forwards: Ryan Baird, Finlay Bealham, Tadhg Beirne, Caelan Doris, Tadhg Furlong, Cian Healy, Rob Herring, Cormac Izuchukwu, Oli Jager, Ronan Kelleher, Joe McCarthy, Peter O'Mahony (capt), Tom O'Toole, Andrew Porter, Cian Prendergast, James Ryan, Dan Sheehan, Nick Timoney, Josh van der Flier
Backs: Bundee Aki, Caolin Blade, Craig Casey, Jack Crowley, Ciaran Frawley, Robbie Henshaw, Jordan Larmour, James Lowe, Stuart McCloskey, Conor Murray, Calvin Nash, Jimmy O'Brien, Jamie Osborne, Sam Prendergast, Garry Ringrose, Jacob Stockdale