David Cameron has promised an all-out by-election fight against Ukip after one of his MPs dramatically defected to the Eurosceptic party.
The Prime Minister said the decision by Douglas Carswell was "deeply regrettable and counterproductive", arguing that only a Tory government could deliver an in-out referendum on British membership.
The response came after Mr Carswell delivered his bombshell at a hastily arranged press conference, accusing Mr Cameron of being "insincere" and not "serious about real change".
He said he was resigning from the Commons immediately to trigger a contest in his Clacton constituency - where only his personal following is thought to have been holding back the Ukip vote.
A host of Eurosceptic MPs have been deployed to back the party leadership and pour cold water on the possibility of other prominent defections to Nigel Farage's party.
But the jubilant Ukip leader hailed Mr Carswell's decision as the "bravest, most honourable and noblest" he had witnessed in British politics, describing him as a "perfect fit".
Mr Cameron, in Scotland to deliver a speech, told the BBC that Mr Carswell's action was "self-defeating".
"It is obviously deeply regrettable when these things happen and people behave in this way. But it is also, in my view, counter-productive," he said.
"If you want a referendum on Britain's future in the EU, whether we should stay or go, the only way to to get that is to have a Conservative government after the next election.
"That is what until very recently Douglas Carswell himself was saying."
He added: "Obviously I'll want to make sure (that there is) a very strong Conservative campaign in that seat, so they can be properly represented in this Government, and hopefully the next."
Mr Carswell beat the Labour incumbent by just 920 votes to become MP for Harwich in 2005, but won the seat with a 12,000 majority in 2010 - although boundary changes had seen it renamed Clacton.
Ukip performed well in the area in recent local and European elections, and experts believe it will be a big challenge for the Tories to hold on.
However, there is a potential obstacle in the form of Roger Lord - who has already been selected as the Ukip general election candidate for Clacton - and is signalling that he is not willing to stand aside in favour of his erstwhile opponent.
Setting out a litany of criticism of Mr Cameron this morning, Mr Carswell said he did not believe the EU policy was "sincere", saying the leadership wanted to secure "just enough" to pretend change was happening.
"No-one cheered David Cameron's Bloomberg speech more loudly than me ... but there's been nothing since. They haven't thought it through.
"There is a world of change and opportunity out there ... ministers are simply not up to giving us the kind of realignment we need."
Mr Carswell said it would have been easier for him to "muddle along" as a Tory backbencher until next May, but he wanted to do the "honourable" thing.
"As someone who's always answered directly to the independent-minded people of Essex, there is only one honourable thing for me to do," he said.
"I must seek permission from my boss, the people of Clacton. I will now resign from Parliament and stand for Ukip in the by-election that now follows."
Mr Farage said: "I don't think it is any great secret there are now a number of MPs sitting on the Conservative benches, and indeed some now sitting on the Labour benches, who hold Ukip's views very strongly.
"It was only a matter of time before one of them had the courage to come across, at least that is what I thought a couple of years ago.
"I have to say I had begun to wonder whether it would happen, but it has happened.
"And it hasn't just happened in terms of the defection, but I think what makes this all the more dramatic is the fact that Douglas Carswell is prepared to test this with his constituency."
Tory backbencher Zac Goldsmith, who has worked closely with Mr Carswell to demand measures so voters can recall MPs, said the defection should be a "wake-up call" and the move was avoidable.
He said Mr Carswell was a "model Parliamentarian", adding: "I have nothing but admiration for him."
Senior backbencher Bernard Jenkin, whose seat neighbours that of Mr Carswell, told BBC Radio 4's World At One that the defection had come as a "bolt from the blue".
"Douglas will regret making this move because the more Tory voters defect to Ukip, the more likely it becomes that Ed Miliband becomes prime minister," he said.
Fellow Eurosceptics Mark Pritchard and Bill Cash also indicated that they disagreed with the action, while Clacton Conservative Association chairman Simon Martin-Redman said: "We are disappointed and surprised that Douglas Carswell has chosen to stand down. I am a deep-seated Conservative and so are my management team.
"We feel let down and believe it's a regrettable and counter-productive decision since, as he himself has said, the only way to get a referendum on the EU is to return a majority Conservative government.
"We are determined to keep this constituency Conservative."
It is thought the earliest a by-election could happen is October 2 - the day after Mr Cameron is due to deliver his keynote speech to the Conservative Party conference.
Labour leader Ed Miliband said: "Douglas Carswell's defection is not just a blow to David Cameron. It shows the Tory Party is too divided to stand up for hard-working families."
Ukip's only representation in the Commons to date came when Castle Point MP Bob Spink defected from the Conservatives in 2008, although he subsequently stood unsuccessfully as an independent at the 2010 general election.
In May, Mr Carswell attended a seminar hosted by academic Matthew Goodwin, and was told that Clacton is the seat with the population most likely to be receptive to Ukip. According to the assessment, that is because it has a higher proportion of old, poor and white voters who have no academic qualifications.
Previously experts believed a Ukip victory was "almost impossible" because of Mr Carswell's majority and appeal to Eurosceptic voters.
But Mr Goodwin told the BBC: "He will not struggle at all to win an election under the Ukip banner.
"It's classic, left-behind territory for Ukip.
"Douglas Carswell has spent years cultivating an image for himself as being away from the Westminster elite."
A Ukip spokeswoman said: "Roger Lord has never been the by-election candidate for Clacton.
"By-election rules determine that the party is entitled to start with a clean slate of nominations for Prospective Parliamentary Candidates, with the final elected candidate being decided by the National Executive Committee.
"There will not be a hustings in these circumstances as the immediacy of selection that a by-election warrants permits, in accordance with the party's constitution and sensible procedure, for the National Executive Committee to overrule and finitely determine who should represent the party for the campaign.
"Roger Lord is a committed member of Ukip and we appreciate his contribution to the development of the party locally and hope that he understands the decision of the NEC to support Douglas Carswell in the defence of his seat, as a Ukip candidate. "
Conservative MP Jacob Rees-Mogg said he felt Mr Carswell had made a mistake - insisting his friend had won most of his arguments inside the Tory party.
He told the BBC Radio 4 PM programme: "I think Douglas has made a mistake, partly because of what he achieved in the Conservative Party. Douglas is an articulate and intelligent eurosceptic, one of the first MPs to call for us to quit the European Union and the party was moving inexorably towards his position.
"I rather feel he has left at the point he was winning the battle for ideas inside the Conservative Party.
"Ultimately I think this single resignation won't many any difference. If there would be more, it would be very important but as a one-off, in three months time people will have broadly forgotten."
Tory MP Michael Fabricant told PM: "It doesn't encourage me (to defect) ... although I have some similar views to Ukip in Europe, that has to be the truth of the matter, but I have very different views from Ukip on so many other matters.
"I doubt (others will follow) but I was surprised by Douglas Carswell."
Prominent eurosceptic Tory MP Bill Cash said he disagreed with Mr Carswell's move, despite voting with him on most issues.
He told Channel 4 News: "The best way to guarantee we don't have a referendum is to have a Labour or a Lib Dem coalition. That would mean we didn't have a referendum.
"Those who vote for Ukip ... mean the Conservative Party would be destroyed by defectors to Ukip preventing us from winning the marginal seats.
"Every constituency has to be taken on its own merits. There are particular issues in the Clacton context which will come out in that election. I'm by no means convinced Douglas Carswell will win there.
"I really do think Ukip, under first past the post, have a real struggle on their hands to get even one seat, let alone two or three - but even if they do, it doesn't amount to a majority in the House of Commons. In order to have a referendum Act, you have to have a majority of MPs voting for it."