Wales coach Warren Gatland today confirmed Luke Charteris, James Hook, Dwayne Peel, Martyn Williams will all miss the Principality Building Society Summer Test against South Africa at the Millennium Stadium and also the tour of New Zealand in June.
Newport Gwent Dragons lock Charteris is currently recovering from a neck problem, while Hook will be out of contention as soon as his domestic season with the Ospreys ends as he intends to undergo surgery on his shoulder.
Sale Sharks scrum half Peel is deemed to need rest, recuperation and a solid pre-season after well documented injury problems and Cardiff Blues flanker Williams is another player who also needs a break.
After talks with the Wales Team management and medical team, it has been decided Williams will be unavailable for the three Tests in June as he targets a fourth Rugby World Cup in 2011.
But despite the four absentees, Gatland insists his squad for next month's triple-Test mission will be as close as possible to full strength. Gatland will announce his squad online at www.wru.co.uk on Sunday, 16th May.
"We have some depth in these positions with the likes of Jamie Roberts, Andrew Bishop and Jonathan Davies playing well at the moment at centre," said Gatland.
"We are okay in the second row as well, and Sam Warburton has been pushing Martyn really hard for a back row spot at the Blues as well as at international level.
"South Africa in Cardiff, and then two Tests in New Zealand, means we have a tough summer ahead of us. But this is exactly the position we need to be in and it will be perfect preparation for the World Cup."
The WRU has sold approximately 50,000 tickets to date for Wales' clash with the Springboks at the Millennium Stadium on Saturday, 5 June (kick-off 2.30pm) and Gatland is hoping fans will fill the Stadium to its rafters to give his side the send off they need before they depart to his native New Zealand.
"Games don't come much tougher than playing the world champion South Africans and Peter de Villiers has a wide range of talent to choose from," he said.
"Depending on what happens in the Super 14, certain players will be ruled out. But we will be expecting the European-based players like Butch James to figure and Sharks players are likely to be available, so there will be World Cup winners throughout the squad.
"They are going to be strong, but it could also be a great day for Wales. If we could win that game it would be a great platform for our summer tour.
"As for New Zealand, we just need to believe in ourselves and perform like we know we can. Then we will have a chance. France won a game there last year and Ireland ran them close as well, so we know it can be done.
"But we are also keen to familiarise the players with our World Cup venues and training bases. It's not until I left New Zealand that I realised that it is such a difficult place to tour and we want the players to have that experience, training at the same venues and staying in the same hotels as we will in 2011."
Tickets for the Principality Building Society Summer Test against South Africa are currently on public sale and are selling fast.
Priced at £25 per person or £80 for a family ( 2 adults, 2 children) tickets for the 'Principality Building Society Summer Test' can be purchased from at the WRU's Cardiff Arms Store (No 8 Westgate Street, Cardiff); via Ticketmaster (tel 08442 777888, www.ticketmaster.co.uk), Ticketline (02920 230130, www.ticketlineuk.com) and via the WRU Official Website www.wru.co.uk/tickets.
The remaining WRU hospitality packages can be snapped up from £119 for the 'SA Gold' package and fans should act fast to secure the hottest tickets via the official website www.millenniumstadium.com.
Further hospitality information is available online for all packages including the 'Platinum Suite' at £229 and the recently launched after popular demand. 'Springbok Suite' at £139.
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Bedwas head coach Steve Law and players Nicky Griffiths and Alun Rees extol the virtues of the close knit club as they prepare to host third place RGC 1404 - who are one place head of them on the Principality Premiership points table - on Saturday.
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