Wales playmaker Aaron Ramsey is out of the must-win Euro 2020 qualifier with Azerbaijan on Friday week.
The FA of Wales announced the news at Tuesday lunchtime, Ramsey having been left out of new club Juventus' opening day Serie A win over Parma.
Ramsey is still fighting his way back from a hamstring injury and did not make Maurizio Sarri's match-day squad.
The ex-Arsenal man had donned the black and white shirt for the Italian champions in a pre-season friendly against Triestina, when he made his debut after coming on for the last 20 minutes.
That was his first game of football since mid-April following an ongoing hamstring problem, but it seems he is still not deemed fit enough for international action.
News of the loss of Ramsey comes as a huge blow to boss Ryan Giggs, who has grudgingly ruled out the Juventus man.
He has already been without his midfield kinpin for the three opening Euro clashes with Slovakia, Croatia and Hungary and needs Ramsey's flair back in the team.
However, Ramsey's lack of competitive game time is viewed as an area of concern by Wales.
Giggs has chosen to replace Ramsey in the squad with highly-rated Manchester United youngster Dylan Levitt, who steps up from the under-21s.
Wales have to beat Azerbaijan to retain any hope of qualifying from their group.
Although Juventus don't yet view Ramsey as fit enough for league action, he recently said: "I feel good. I have had a good rehab so hopefully I can stay fit — and help the team as much as I can.
“It was a very proud moment for me to put on this famous jersey against Triestina.
“I feel good physically and I’ve had a good pre-season.”
After Azerbaijan, Wales have a friendly game against Belarus. Ramsey was never likely to feature in that one, though.
