Wales tighthead prop Adam Jones has been ruled out of his country's November internationals due to a knee injury.
Jones aggravated the knee problem, which he originally suffered in September, while playing for Ospreys in their European Cup defeat at Leicester last weekend and the damage is significant enough to make it impossible for him to recover in time for the Tests against Argentina, Samoa, New Zealand and Australia.
"Adam Jones has withdrawn from the 35-man Wales squad due to a knee problem," a statement on the Welsh RFU's website confirmed.
"The Ospreys prop will undergo a rehabilitation period of between six to 10 weeks, with regular assessments to establish an accurate return, effectively ruling him out of Wales' clashes with Argentina, Samoa, New Zealand and Australia at the Millennium Stadium, beginning next month.
"Jones will also miss the national squad training camp in Spala, Poland, which departs this weekend, after being reviewed by his orthopaedic consultant today (Friday)."
The absence of Jones, a three-time Grand Slam winner who has 83 caps, is a major blow to Wales' hopes of a successful run in the internationals.
The 31-year-old's injury means his Ospreys teammate Aaron Jarvis has a chance to make his Wales debut.
Teenage Scarlets prop Samson Lee has been called up as cover, while Scott Andrews is the other specialist alternative.
"Adam has been struggling with his knee for four or five weeks now," Ospreys forwards coach Jonathan Humphreys said before his absence was confirmed.
"He's put the team first, he's played through a bit of pain, but on the weekend he re-injured that area.
"It's an area in the past that Wales haven't had a lot of strength in, but hopefully Aaron will get some game time, some opportunities and push his claim forward."
Wales host Argentina on November 10, then face Samoa on November 16 and New Zealand on November 24 before concluding their schedule against Australia on December 1.