Johnny Sexton is facing up to 3 months out of action after undergoing shoulder surgery.
The out-half is replaced by Ian Madigan in the Ireland squad for the tour of South Africa.
Sexton suffered the injury in the province’s 20-10 loss to Connacht in the Guinness Pro12 final at Murrayfield.
The 30-year-old went under the knife in an effort to repair the damage to his shoulder on Tuesday.
Full-back Rob Kearney misses out with a hamstring injury, a calf problem means his brother Dave is also sidelined for the tour.
Connacht's Tiernan O'Halloran and Ulster's Craig Gilroy have been drafted into the squad as replacements.
Matt Healy takes the place of the injured Luke Fitzgerald. The first of the three Tests against the Springboks is on June 11th.