Wales have suffered a second major injury blow ahead of Saturday's RBS 6 Nations opener against England.
British and Irish Lions prop Gethin Jenkins has been ruled out of the Twickenham showdown after failing a fitess test this afternoon on a calf muscle problem.
Ospreys forward Paul James is promoted from the bench to replace Jenkins, with uncapped Saracens prop Rhys Gill named on the bench instead of James.
Jenkins' withdrawal follows the loss yesterday of his fellow Lion and front-row forward, hooker Matthew Rees, whose groin injury sidelined him from Wales coach Warren Gatland's selection plans.
Gatland said: "Obviously, it is not ideal for us to lose Gethin at this stage, and we wish him a speedy recovery.
"Paul James has been one of the form props in the Welsh regions so far this season, and we are confident he will be a more than able deputy for Gethin."
James, 27, started all four of Wales' autumn Tests this season as a tighthead prop replacement for Adam Jones. Loosehead, though, is his familiar position for the Ospreys.
Jones is now back after recovering from a serious shoulder injury suffered on the Lions tour of South Africa last summer.
But Gatland's hopes of fielding an all-Lions Test front row opposite an inexperienced English trio have been decimated.
Wales, with 72 times-capped Jenkins and Rees packing down alongside the destructive Jones, would have been expected to make life distinctly uncomfortable for an England front row of Tim Payne, Dylan Hartley and David Wilson.
It is a task, though, that now lies with Jones, James and Cardiff Blues hooker Gareth Williams - whose last Six Nations start was almost seven years ago.
Jenkins will remain with the Wales camp and be reassessed next week.
Wales' second Six Nations game is against Scotland at the Millennium Stadium in nine days' time.