Former foreign secretary Lord Geoffrey Howe has claimed David Cameron is losing control of his party as the Conservatives' "long, nervous breakdown" over Europe continues.
Lord Howe, whose differences with Baroness Thatcher over Europe led to his resignation and triggered her downfall, said Mr Cameron had "opened a Pandora's box politically" through his plan to renegotiate the UK's relationship with the European Union.
In a strongly-worded attack he said the Tory leadership was "running scared" of its backbenchers and had allowed Euroscepticism to "infect the very soul of the party".
Writing in The Observer, Lord Howe said the row over the lack of legislation paving the way for the Prime Minister's referendum by 2017, which led to a total of 116 Tories opposing the Government's legislative programme, marked a "new, almost farcical, low" for the party. He wrote: "Sadly, by making it clear in January that he opposes the current terms of UK membership of the EU, the Prime Minister has opened a Pandora's box politically and seems to be losing control of his party in the process.
"The ratchet-effect of Euroscepticism has now gone so far that the Conservative leadership is in effect running scared of its own backbenchers, let alone Ukip, having allowed deep anti-Europeanism to infect the very soul of the party. The risk now is that, if it loses the next general election - a far from negligible possibility - the Conservative party will move to a position of simply opposing Britain's continued membership, with or without a referendum."
Lord Howe said the United States looked to the UK to play a leading role in Europe and leaving the EU would "be a tragic expression of our shrinking influence and role in the word". The former chancellor added it would represent "the humbling of our ambitions, already sorely tested by the current crisis, to remain a serious political or economic player on the global stage". He claimed "clear thinking" and "strong leadership" was needed to protect the UK's status within the EU.
Health Secretary Jeremy Hunt insisted the Tory party was "absolutely united" on the issue of Europe and Lord Howe's views did not "represent the reality" of the situation.
He told BBC1's Andrew Marr Show: "If you look at the substance of the issue, the Conservative Party is absolutely united. We look at the European Union and we worry about Britain's ability to compete in the global race, we look at the regulations and the red tape that comes from Europe, yesterday some new regulation about selling olive oil in restaurants. If you go into the boardrooms in New York or Tokyo or Singapore they think the European economy is frankly a joke."
Mr Cameron was "showing leadership" on Europe by promising to work to change the relationship with Brussels and the Tories were the only party prepared to "do the heavy lifting on this".
Mr Hunt added: "Of course we have a debate. Patriotism runs deep in the veins of all Conservatives and when you have an issue of sovereignty it's something we debate fiercely." But he said "don't underestimate David Cameron" because he had shown through his use of the veto and securing a cut in the EU budget "this is someone who has delivered a very great deal".