Manchester's famous Boddingtons brewery is to close with production switched to Lancashire, Wales and Scotland.
Unions say the move from the landmark brewery is a "betrayal"
But its Belgian parent company Interbrew says it wants to maintain cask production in the city.
The brewery will shut in 2005 with the loss of 55 jobs as production switches to Samlesbury, Lancashire, Magor, south Wales, and Glasgow.
Union leaders have pledged to repeat a campaign they waged two years ago when closure plans were first mooted.
On that occasion, a deal was brokered which saved the plant and jobs.
Interbrew said it was moving production of non-cask beers, such as Boddingtons Draught nitrokeg and Gold Label Strong Ale, to other sites to cut distribution costs.
They make up 90% of production at the Strangeways brewery in Manchester.
The Transport and General Workers' Union (T&G) said managers at the plant broke the news at 0700 BST on Thursday.
T&G official Phil Thompson said the plans were a "gross betrayal", adding: "We can't get a grip of what's going on, especially as sales are up."
Mr Thompson, who said Interbrew were quick to promote the beer as the "Cream of Manchester" when the Commonwealth Games were taking place in 2002, vowed to fight the decision.
He said that last time the brewery was under threat workers had support from drinkers all over the UK, MPs, the Campaign for Real Ale and expatriate Mancunians all over the world.
Boddingtons is advertised as the Cream of Manchester
Franny Joyce, North West regional organiser for the T&G, said: "People are shocked and angry. This is a
complete betrayal of the workforce.
He called plans to continue making casks in Manchester "a con", as the work accounted for only 10% of the production at Strangeways.
"If they pull out of Manchester, the brand will die. It won't be the Cream of Manchester, it will become the sour grapes of
Interbrew said it hoped to move cask production to the Hydes Brewery in the Moss Side area of Manchester.
Chief executive Steve Cahillane said: "To reach this position on the Boddingtons brewery has been extremely difficult, particularly because of the tremendous commitment shown by all of the employees at the brewery.
"But in a highly competitive environment, it is just not sustainable to continue brewing keg ales at Boddingtons and then transport them to our other brewery sites for packaging, when those sites already have the brewing capacity in place."
Boddingtons has been brewed in the city since 1778 and its brewery in Strangeways, just north of the city centre, is one of Manchester's best-known landmarks.
The firm based its advertising campaigns since the late 1980s around the city, most famously with an actress drinking a pint while travelling on a gondola along the Rochdale Canal.