Wales prop Adam Jones and fly-half James Hook have both been left out of a 34-man squad for next month's Tests against Australia, Fiji, New Zealand and South Africa.
The Welsh Rugby Union has announced a group that includes one uncapped player - 20-year-old Ospreys prop Nicky Smith - with flanker Sam Warburton confirmed as captain.
Cardiff Blues forward Jones and Gloucester back Hook have more than 170 caps between them, but can find no place in Wales head coach Warren Gatland's squad.
Jones, 33, has won 95 Wales caps and played in five Tests for the British and Irish Lions. He joined Cardiff Blues from the Ospreys earlier this year.
Hook, 29, is also a Lion and has played in a number of positions behind the scrum for Wales, but both have failed to make Gatland's cut for a demanding series of games less than a year out from the Rugby World Cup.
Smith is among six props named in the squad - Gethin Jenkins, Paul James, Samson Lee, Aaron Jarvis and Rhodri Jones are the others - with Hook's versatility not enough to catch Gatland's eye.
There is a recall for Wasps lock Bradley Davies, who has been in outstanding form this season, with Wales' France-based players Leigh Halfpenny, Jonathan Davies, Jamie Roberts, Mike Phillips, Luke Charteris and Dan Lydiate also taking their places, as expected.
Others to miss out, though, include fleet-footed Ospreys wing Eli Walker, Cardiff Blues hooker Matthew Rees and his Blues colleague, fly-half Rhys Patchell.
"We are really happy with the squad," Gatland said.
"There is a lot of experience that has come back in, 12 players who were injured in the summer and didn't tour South Africa. They are back and fit and we have a couple of exciting youngsters as well.
"Nicky Smith has been playing exceptionally well for the Ospreys. We have been impressed with him and it's a great opportunity.
"When you look through the squad there is a huge amount of experience.
"We've taken a lot of things into account and made some tough decisions.
"We've had to weigh up a balance of players who play in Wales and outside, due to how often they can train and are with us, but we are really happy with the squad.
"We are looking to the future and the next 12 months ahead with this squad, but it doesn't close the door for anyone not selected."
Gatland's final comment will give a glimmer of hope to both Jones and Hook, but they would now appear to be up against it in terms of gaining RBS 6 Nations recognition later this season, and also moving ahead to the World Cup.
Wales squad for November Tests against Australia, Fiji, New Zealand and South Africa:
Backs: L Williams (Scarlets), L Halfpenny (Toulon), T Prydie (Newport Gwent Dragons), G North (Northampton), A Cuthbert (Cardiff Blues), H Amos (Newport Gwent Dragons), S Williams (Scarlets), J Davies (Clermont Auvergne), J Roberts (Racing Metro), C Allen (Cardiff Blues), R Priestland (Scarlets), D Biggar (Ospreys), M Phillips (Racing Metro), R Webb (Ospreys), R Williams (Scarlets).
Forwards: G Jenkins (Cardiff Blues), P James (Bath), N Smith (Ospreys), A Jarvis (Ospreys), S Lee (Scarlets), R Jones (Scarlets), R Hibbard (Gloucester), E Phillips (Scarlets), S Baldwin (Ospreys), A-W Jones (Ospreys), J Ball (Scarlets), B Davies (Wasps), L Charteris (Racing Metro), D Lydiate (Racing Metro), J King (Ospreys), S Warburton (Cardiff Blues, capt), J Tipuric (Ospreys), D Baker (Ospreys), T Faletau (Newport Gwent Dragons).