Robin Cook, the leader of the Commons and a former foreign secretary, today resigned from the government in protest over the prime minister's stance on Iraq.
Following a weekend of fervent speculation - and silence from Mr Cook himself - the minister left Downing Street before the start of today's emergency cabinet.
Mr Cook said in a statement: "It is 20 years ago that I first joined Labour's shadow cabinet. It is with regret I have today resigned from its cabinet. I can't accept collective responsibility for the decision to commit Britain now to military action in Iraq without international agreement or domestic support."
He becomes the first - but possibly not the last - cabinet minister to resign over the looming conflict in the Gulf. The international development secretary, Clare Short, is "reflecting overnight" on her position, a spokeswoman from her department said.
Mr Cook is now expected to make a public statement on his resignation in the Commons tonight, following Jack Straw's address to MPs at 7pm.
This could be a highly dramatic moment, as Mr Cook is a veteran Commons orator, and is expected to take apart the legal basis for a pre-emptive attack on Iraq with forensic skill.
In his letter of resignation, Mr Cook made clear that he had raised his worries over a US/UK attack over some time with the prime minister - although absolved Mr Blair from blame for the failure of the UN to secure a second resolution.
He wrote: "At cabinet for some weeks I have been frank about my concern over embarking on military action in the absence of multilateral support.
"In principle I believe it is wrong to embark on military action without broad international support. In practice I believe it is against Britain's interests to create a precedent for unilateral military action.
"As our foreign secretary I was impressed by the energy and skill with which you ended Britain's isolation in Europe and achieved for our country equal status and influence to Germany or France. I am dismayed that once again Britain is divided from our major European neighbours.
"As president of the party of European socialists, of which the Labour party is a member, it troubles me that I know of no sister party within the European Union that shares our position."
Mr Blair, in response, praised Mr Cook's time as foreign secretary and leader of the Commons, but used the majority of his letter to justify the government's position - largely blaming the French.
He wrote; "I want to thank you for the contribution you made in your two cabinet posts, and no doubt will continue to make, to forging better relations between Britain and the rest of the EU. When the current crisis is over, this will be particularly important.
"On your resignation, I have always tried to resolve this crisis through the UN, as you recognise in your letter. But I was always clear that the UN must be the way of dealing with the issue, not avoiding dealing with it.
"The government is staying true to resolution 1441. Others, in the face of continuing Iraqi non-compliance, are walking away from it.
As I have said to you, the threatened French veto set back hugely the considerable progress we were making in building consensus among UNSC members. "
Mr Cook's colleague, Clare Short, the international development secretary, last week threatened to quit the government if an attack on Iraq took place without a second UN resolution.
Mr Cook's position as leader of the Commons, where he has done much to modernise MPs working hours while losing the battle for a more democratic upper chamber, can be easily filled - most probably by the current chief whip, Hilary Armstrong. However, the political significance lies in Mr Cook's five years as Mr Blair's first foreign secretary, the post now occupied by Jack Straw.
A PPS to Margaret Beckett, Andy Reed, has already quit over Iraq, and Mr Blair has survived a rebellion by 122 Labour backbenchers, all of whom voted for a motion saying the case for war on Iraq was "not proven".
Although the Conservative frontbench has pledged its support for the prime minister's position of allying Britain to a US-led attack on Iraq, several high-profile backbench Tories have come out against military action, including former chancellor Kenneth Clarke.
A Conservative junior whip, John Randall, has also resigned his post in the party.
Mr Cook's Commons deputy Ben Bradshaw was seen going into Downing Street before the cabinet meeting and speculation was that he will be asked to make a brief business statement to MPs outlining the timetable now the peace process with Iraq has been abandoned and war could begin.
Mr Cook's decision to quit the cabinet will cost him almost £70,000 a year in lost pay.
As Leader of the House of Commons he was entitled to a salary of £124,979. As a plain backbench MP, his salary will be £55,118 a year.
The former culture secretary Chris Smith mourned the resignation of Mr Cook, saying having the former Commons leader on the backbenches left the government "diminished."
Downing Street later announced it would publish in full the letters of correspondence between the prime minister and Mr Cook.
The shadow foreign secretary, Michael Ancram, said: "While we understand Robin Cook's reasons for resigning, disunity within the cabinet is a matter of concern at this time.
"We hope the prime minister will take further steps to ensure that his cabinet speaks with one voice."
The Liberal Democrats' foreign affairs spokesman, Menzies Campbell, said: "It was always likely that Robin Cook, who sought to introduce an ethical dimension into foreign policy, would find the ambiguity of the government's position too much to tolerate."
Paul Tyler, who speaks on House of Commons affairs for the Liberal Democrats, added: "The government has lost its most effective Commons performer. His leadership of the Commons gained him an unrivalled reputation amongst fellow members.
"I have no doubt he will be a formidable presence on the backbenches."
A handful of protesters shouting "Blair out" brought Whitehall to a standstill outside the gates to Downing Street as the cabinet met in emergency session.
Police blocked off one side of the carriageway as the few protesters waved placards and blew whistles.