The former Chancellor Lord Geoffrey Howe has accused the Prime Minister of "losing control" of his party following a turbulent week in which divisions over European policy came to the fore.
Writing in the Observer, Lord Howe said the Conservative leadership was "running scared" of its own backbenchers and had allowed "anti-Europeanism to infect the very soul of the party".
The criticism comes days after 114 Tory MPs defied the party line by voting for an amendment to the Queen's Speech expressing regret that an EU referendum bill was not included in the government's legislative plan.
Health Secretary Jeremy Hunt insisted that the party was "absolutely unified" on its European strategy and that Lord Howe's portrayal did not "represent the reality" of the situation.
ITV News correspondent Romilly Weeks reports:
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 EU:
– Lord Howe
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.
Conservative leaders, including the Prime Minister, have denied that last week's vote represented a rebellion, arguing that it was a free vote for all parliamentarians below the ministerial level.
But one eurosceptic MP, John Baron, told ITV News that he and his fellow backbenchers would not rest until they had legislation on an EU referendum.
Speaking on BBC1's Andrew Marr show, Jeremy Hunt said the party was unified around the substance of Mr Cameron's European strategy:
The Conservative party is already reeling from unsubstantiated reports in two newspapers that an aide close to the Prime Minister described local Tory activists as "mad swivel-eyed loons".
The senior figure is reported to have said: “There’s really no problem over the vote for an amendment]. The MPs just have to do it because the associations tell them to, and the associations are all mad swivel-eyed loons.”
Downing Street has described the reports as "categorically untrue" and one senior party official condemned false rumours that he was behind the remarks.
A ComRes poll for The Independent on Sunday, shared with the Sunday Mirror, showed that UKIP has reached its highest ever vote share of 19 percent.
It also showed the Prime Minister's lowest ever approval rating at just 26 percent.