Wales will aim to end 20 years of hurt at Twickenham next week - and new coach Warren Gatland insists he has "no fear" about the challenge ahead.
While the England camp continues taking every precaution to ensure the mumps virus that has affected wing Paul Sackey does not spread, Wales aim to inflict a debilitating defeat on last year's World Cup finalists.
England, who have not lost to Wales at Twickenham since 1988, will be hot favourites for an opening weekend RBS 6 Nations victory.
But Gatland, who is about to make a Test bow as Wales boss, knows his players cannot suffer from an inferiority complex.
Gatland said: "We will have a list of things as a squad we want to achieve - one of them is to win at Twickenham. If it doesn't happen this year, then in the next few years.
"You have to go out there with some self-belief. If you have any doubts, then Twickenham is a long day at the office.
"But England as a squad holds no fear for me. There are a lot of players I know really well. There are strengths and weaknesses of a number of England players.
"They hold no fear for me, and I have to instil that into my players.
"For us, the first few games will be getting the basics right, and the basics are our defence, our scrum, line-outs, driving and mauling play and the contact area.
"If we can get that to a reasonable level, then we can start developing the game we want to play.
"I am confident we can put a good side together. I am impressed by the potential of the athletes we have to work with."
England, meanwhile, have confirmed London Irish scrum-half Peter Richards will miss the whole of the tournament after undergoing an operation to repair a torn bicep muscle.
Richards was injured during the Exiles' European Cup win over Treviso last Saturday, and will be out of action for three months.
England head coach Brian Ashton now faces a straight choice between World Cup number nine Andy Gomarsall and uncapped Sale Sharks prospect Richard Wigglesworth to face Wales.
Elsewhere, Wasps, Gloucester and England players were given the MMR vaccine after it was confirmed that Sackey has contracted mumps.
Sackey was withdrawn from Wasps' Heineken Cup clash against Munster in Limerick last Saturday after showing the early symptoms. He was immediately placed into quarantine, and a saliva test on Monday confirmed the diagnosis.
Wasps doctor David Ward and his England counterpart Simon Kemp have been working closely with the Health Protection Agency to minimise any risk of a mumps outbreak among Guinness Premiership players.
Dr Kemp said: "We believe that all possible and practical strategies to reduce the risk of further infection are being taken."
Sackey is expected to cease being contagious within the week, at which point he will come out of quarantine and be available to link up with the England squad.
England Under-18 head coach John Fletcher insists his young side will be better for the experience after beating Italy in the bronze final to round out their 2015 Rugby Europe U18 Championship campaign in style.