England's chances of producing three semi-finalists in the Champions League for the third successive season were dented on Friday by a tough-looking last 16 draw.
Holders Manchester United were paired with Italian champions and Serie A leaders Inter Milan while Premier League leaders Liverpool take on nine-times champions Real Madrid after the draw was made at UEFA headquarters in Nyon, Switzerland.
Last year's runners-up Chelsea were paired with Juventus, managed by former Blues boss Claudio Ranieri, while Arsenal, finalists in 2006, play AS Roma in a third Anglo-Italian clash.
The Manchester United tie will see another former Chelsea boss, Jose Mourinho, returning to face Premiership opposition in his new role in charge of Inter.
"Obviously Jose has put us out of the competition before," said United's communications director Phil Townsend in reference to Mourinho's success at the same stage in 2004 with eventual European champions Porto.
"But equally we put Inter out in 1999 when we went on to win the tournament so maybe that's a good omen for us."
Real Madrid's meeting with Liverpool will mark only the second time that the Spanish nine-time European champions have met the English five-time winners in the competition.
Their only previous encounter came in the final of the 1981 European Cup with Liverpool winning 1-0.
"It's mammoth, it really couldn't be a much bigger tie and I think our fans will be absolutely delighted that we've picked them up at this stage of the competition," said Liverpool club secretary Bryce Morrison.
Liverpool boast by far the better form as Premier League leaders while Real languish sixth in the Primera Liga, a daunting 12 points behind leaders Barcelona.
"The problem at our club is that we have had a lot of injured players but there is plenty of time for them to recover before we play Liverpool in February," said Real Madrid director Jose Luis Lopez Serrano.
"There is a great relationship between the two clubs and I'm sure there will be two very interesting games in Madrid and Liverpool. It will be difficult for us to get through obviously but I think it will also be difficult for them."
Chelsea secretary David Barnard played down talk of Ranieri having the chance to take revenge against his former employers.
"I don't think 'revenge' will be the right word for Claudio's return because he was given a great reception by the fans when he left the club and I'm sure he'll get one when he comes back," Barnard told Reuters.
"He'll know a lot of our players of course and the fact Juve got to the knockout stage shows that they're a quality team."
Barcelona, the only non-English side to reach the semi-finals last season, play Olympique Lyon, who are in the knockout phase for the sixth successive season.
Villarreal, who reached the semi-finals in their first appearance in 2006, drew Panathinaikos while the other pairings were Atletico Madrid v Porto and Sporting v Bayern Munich.
The ties take place on Feb. 24/25 and March 10/11 with the final on May 27 in Rome.