Ireland skipper Keith Wood has lost his fitness fight ahead of Sunday's Lloyds TSB Six Nations opener with Wales in Dublin.
Wood - IRB international player of the year - conceded defeat after failing to turn out for Harlequins in their Zurich Premiership match against Northampton at the weekend.
His calf muscle injury has been slow to heal and his withdrawal from the Irish squad was confirmed today.
It is part of a double blow for new Irish coach Eddie O'Sullivan ahead of his first competitive match in charge.
O'Sullivan must also plan without lock Malcolm O'Kelly, who missed Leinster's Heineken Cup defeat at Leicester yesterday with a fractured cheekbone and will not be fit in time to face the Welsh at Lansdowne Road.
Munster hooker Frank Sheahan will replace Wood in the starting line-up with Leinster's Shane Byrne promoted from the A squad, while Munster's Paul O'Connell as cover for O'Kelly.
Lions centre Rob Henderson has also been called into the senior squad from the Ireland A squad as a precaution should Leinster's Shane Horgan fail to recover from the rib injury he sustained in the Heineken Cup clash at Welford Road yesterday.
PA