Boris Johnson has galvanised the EU referendum campaign with a declaration that he is to join the campaign for Britain to leave.
A day after David Cameron appealed on the steps of Downing Street for voters to back his EU re-negotiation deal, the London mayor said it had failed to deliver fundamental change in Britain's relationship with Brussels.
"I don't think that anybody can claim that this is fundamental reform of the EU or of Britain's relationship with the EU," he said.
His announcement - putting and end to months of speculation - is a huge boost for the Brexit campaign potentially giving them a popular figurehead able to connect with voters in a way few other Westminster politicians can manage.
At the same time, it comes as a bitter blow for David Cameron who had long believed that his old rival from their days at Eton and Oxford would ultimately fall in behind his EU re-negotiation package.
Amid chaotic scenes outside his north London home, Mr Johnson said that he had agonised over the decision.
"The last thing I wanted was to go against David Cameron or the Government but after a great deal of heartache I don't think there is anything else I can do," he said.
Writing in his weekly column in The Daily Telegraph, Mr Johnson said the EU was fuelling political alienation and the rise of extremism as voters witnessed the "impotence" of national elected politicians to deal with issues such as immigration.
"That enrages them; not so much the numbers as the lack of control. That is what we mean by loss of sovereignty - the inability of people to kick out, at elections, the men and women who control their lives," he said.
"We are seeing an alienation of the people from the power they should hold, and I am sure this is contributing to the sense of disengagement, the apathy, the view that politicians are 'all the same' and can change nothing, and to the rise of extremist parties."
His announcement drew a furious response from the Conservative former deputy prime minister Lord Heseltine who warned that a vote to leave the EU would be devastating for the City of London.
"If he were to be successful in his ambition to cut us off from Europe, the flags would fly in Frankfurt and Paris in his honour," he said.
"At a stroke, he would have blown away the safeguards for our financial services industry that the Prime Minister has just secured."
Critics were swift to claim that the real reason for Mr Johnson's announcement was to position himself for a potential challenge for the Tory leadership, saying that he had no track record as an "outer".
Earlier, Mr Cameron - who was reportedly only notified of Mr Johnson's decision in a text sent a few minutes before he made the announcement - had issued a last ditch appeal for him not to align himself with the "out" campaign.
"I think the prospect of linking arms with Nigel Farage and George Galloway and taking a leap into the dark is the wrong step for our country," he told BBC One's The Andrew Marr Show.
"If Boris and if others really care about being able to get things done in our world, then the EU is one of the ways in which we get them done."
The Prime Minister dismissed claims that Brexit would restore sovereignty to the UK, saying in practice Britain was able to exercise far greater leverage internationally from within the EU.
"If Britain were to leave the EU that might give you a feeling of sovereignty but you have got to ask yourself 'is it real?'," he said.
"You have an illusion of sovereignty but you don't have power, you don't have control, you can't get things done."
Opposition parties said Mr Johnson was putting personal ambition ahead of the national interest. Liberal Democrat leader Tim Farron said the mayor had had "more positions on Europe than the Kama Sutra".
"This is a deeply cynical move from a deeply ambitious politician who is using an in-out referendum as a back door to Number 10," he said.
Shadow foreign secretary Hilary Benn said: "Boris Johnson in the past has written a lot about the importance of staying in the European Union and if he is actually thinking about putting his personal leadership ambitions above the national interest I don't think it's going to do him any good."