Ireland skipper Brian O’Driscoll and hooker Rory Best have been ruled out of the forthcoming autumn international series because of injuries.
O’Driscoll picked up an ankle injury in Leinster’s game with Cardiff Blues and scans have shown that he will require surgery to repair ligament damage.
The centre is set to be out of action for eight to 12 weeks.
Best sustained sprained ligaments in his neck while playing for Ulster and will require rest and rehabilitation.
The former Ulster captain suffered the injury in his province’s Pro12 win over the Dragons and his situation wil be assessed again after a period of four to six weeks.
Uncapped Richardt Strauss and Sean Cronin, who has 21 caps, are now set to battle it out for the number two shirt.
Cronin was one of seven players added to the original Irish panel of 31 on Sunday after Irish management reported that several of the squad had suffered knocks while in action for their clubs.
Ulster quartet Craig Gilroy, Paul Marshall, Paddy Jackson and Declan Fitzpatrick were all called up, along with Michael Bent and Tiernan O’Halloran.
News of the absence of two of Ireland’s most senior and experienced players will come as a further blow to coach Declan Kidney, who already had to plan without ERC player of the year Rob Kearney because of a back injury.
O’Driscoll’s injury will also see him miss Leinster’s Heineken Cup games in December, and the Lions star may even face a race against time to make the start of Ireland’s Six Nations campaign in February.
Best must be rated doubtful for Ulster’s crucial Heineken Cup double-header against Northampton on 7 and 15 December.
Ireland begin their autumn series against South Africa in Dublin on 10 November, followed by a game between an Ireland XV and Fiji at Thomond Park a week later.
Argentina visit the Aviva Stadium on 24 November.
Ireland squad: Michael Bent (Leinster), Tommy Bowe (Ulster), Darren Cave (Ulster), Tom Court (Ulster), Sean Cronin (Leinster), Gordon D’Arcy (Leinster), Keith Earls (Munster), Stephen Ferris (Ulster), Declan Fitzpatrick (Ulster), Craig Gilroy (Ulster), Cian Healy (Leinster), Jamie Heaslip (Leinster), Iain Henderson (Ulster), Chris Henry (Ulster), Paddy Jackson (Ulster), David Kilcoyne (Munster), Luke Marshall (Ulster), Paul Marshall (Ulster), John Muldoon (Connacht), Conor Murray (Munster), Mike McCarthy (Connacht), Fergus McFadden (Leinster), Kevin McLaughlin (Leinster), Donncha O’Callaghan (Munster), Paul O’Connell (Munster), Tiernan O’Halloran (Connacht), Ronan O’Gara (Munster), Peter O’Mahony (Munster), Eoin Reddan (Leinster), Mike Ross (Leinster), Donnacha Ryan (Munster), Jonathan Sexton (Leinster), Richardt Strauss (Leinster), Andrew Trimble (Ulster), Dan Tuohy (Ulster), Simon Zebo (Munster).