Johnny Sexton has been ruled out of Ireland's upcoming tour of South Africa, along with brothers Dave and Rob Kearney.
The Leinster fly-half has undergone surgery to repair a shoulder injury he picked up in his province's Guinness Pro12 final defeat by Connacht at Murrayfield last weekend and looks set to be out of action for up to three months.
In total, four Leinster players have been left in the treatment room as a result of that final defeat.
Ireland boss Joe Schmidt confirmed that he has called up Ian Madigan to replace Sexton in the squad with Ulsterman Paddy Jackson now set to start at number 10 against South Africa in the opening test on 11 June.
Full-back Rob Kearney also misses the tour because of a hamstring injury he sustained in training on Wednesday, while his brother Dave is ruled out with a calf muscle injury.
Connacht's Tiernan O'Halloran and Ulster's Craig Gilroy have been called into the squad as replacements.
As expected, a knee injury for Luke Fitzgerald means that he will also remain at home for the tour with Connacht's Matt Healy getting the nod to replace him.
The squad departs for South Africa on Sunday 5 June and will play Tests in Cape Town, Johannesburg and Port Elizabeth. It will be the first time Ireland will tour South Africa in 12 years.
Forwards: Finlay Bealham (Connacht), Rory Best (Ulster, capt), Sean Cronin (Leinster), Ultan Dillane (Connacht), Tadhg Furlong (Leinster), Jamie Heaslip (Leinster, vc), Iain Henderson (Ulster), David Kilcoyne (Munster), Jack McGrath (Leinster), Jordi Murphy (Leinster), Sean Reidy (Ulster)*, Mike Ross (Leinster), Quinn Roux (Connacht)*, Rhys Ruddock (Leinster), Donnacha Ryan (Munster), CJ Stander (Munster), Richardt Strauss (Leinster), Devin Toner (Leinster)
Backs: Keith Earls (Munster), Craig Gilroy (Ulster), Matt Healy (Connacht)*, Robbie Henshaw (Connacht), Paddy Jackson (Ulster), Ian Madigan (Leinster), Kieran Marmion (Connacht), Luke Marshall (Ulster), Conor Murray (Munster), Tiernan O'Halloran (Connacht)*, Stuart Olding (Ulster), Jared Payne (Ulster), Eoin Reddan (Leinster), Andrew Trimble (Ulster)