Ireland centres Brian O'Driscoll and Gordon D'Arcy have been ruled out of Saturday's Six Nations game against Scotland at Murrayfield after both failed to recover from their hamstring injuries.
The centre pairing are considered firm favourites to line up together in Sir Clive Woodward's British & Irish Lions team in the Test against New Zealand this summer and their absence will be of some concern to the Lions coach, who was hoping to use the Six Nations to run the rule over most of his tour prospects.
D'Arcy, 25 on Thursday, was limped out of the 28-17 victory against Italy last week in the 33rd minute after pulling up at full speed.
It looked like he may have recovered in time to face Scotland but he was withdrawn from the squad on Friday morning.
Ireland coach Eddie O'Sullivan said: "We gave Gordon a chance but it didn't work out.
"In terms of the risk element, it was a sensible precaution.
"He should be fine for the next game but we do not want to tempt fate."
Skipper O'Driscoll, who is also favourite to secure the Lions captain's role, was ruled out on Thursday after a fitness test. He was hit from behind in a ruck during injury time of Italy match and was trapped on the floor in the splits position.
A spokesman with the Ireland team said: 'Both players are recovering extremely quickly but they have just six days and it was decided that O'Driscoll will not be 100% ready by the match."