Manchester United were dumped out of English football's League Cup after losing on penalties to second-tier Middlesbrough, who reached the quarter-finals having withstood a late onslaught to secure a 0-0 draw in extra time.
Middlesbrough were clinical in the shootout as hosts United faltered with Wayne Rooney, Michael Carrick and Ashley Young all failing to convert from the spot at Old Trafford.
It was a much better night for two of United's fiercest rivals, new coach Juergen Klopp tasting victory for the first time as Liverpool manager as they beat Bournemouth 1-0 while Manchester City thrashed Crystal Palace 5-1.
Goals have been a priceless commodity for Liverpool this season and it was another nervy night as they scored in the first half through Nathaniel Clyne but could not add to their tally and were forced to hang on for the win.
Goals are rarely in short supply at the Etihad Stadium and City were ruthless as they brushed aside Palace with efforts from Wilfried Bony, Kevin de Bruyne, Kelechi Iheanacho, Yaya Toure (penalty) and Manu Garcia.
There was more woe for managerless Aston Villa who lost 2-1 at Southampton. Maya Yoshida and Graziano Pelle put the hosts two goals up before Scott Sinclair netted a late consolation from the penalty spot.
United became the latest high-profile casualty in the fourth round after Arsenal were knocked out by second-tier Sheffield Wednesday and Chelsea were beaten by Stoke City.
Middlesbrough thought they had scored in the second half when Daley Blind slammed the ball into his own net, only for an offside decision against Kike sparing the Dutchman's blushes.
United should then have wrapped up the contest in extra time but striker Anthony Martial and midfielder Marouane Fellaini missed fantastic chances to head them in front.
Klopp was facing the prospect of going a fourth game without a win since taking over at Liverpool three weeks ago.
Three successive draws had dampened some of the euphoria around his appointment and a number of injuries to first-team players had limited his options, especially in attack.
While City drew a blank at Old Trafford in the Manchester derby on Monday, they reverted to type against Palace as they scored five goals or more for the third time this month.
In the quarter-finals Middlesbrough play Everton, Southampton play Liverpool, Stoke City play Sheffield Wednesday and Manchester City play Hull City.