Ken Clarke has dismissed David Cameron's hints he could lead the 'No' to EU campaign in 2017 as political posturing.
The former chancellor said the Prime Minister could not abandon his pro-European stance, because he would face "derision" and accusations of hypocrisy from voters.
Mr Clarke added that he would "go bananas" if Mr Cameron did back a 'No'.
And he suggested that the Tory leader signed up to the 2017 referendum only because of "party management".
The Prime Minister has hardened significantly his rhetoric on the EU in recent weeks.
He told other European leaders he could "rule nothing out" in the referendum unless they agreed to his demands for a new deal for the UK.
Mr Clarke's comments will infuriate Tory eurosceptics pressing Mr Cameron to say that he will lead the campaign against EU membership.
He told a lunch in Westminster: "(David Cameron) could not conceivably start arguing for a 'No'.
"Most of the public don't believe that the political establishment have a principle in their body.
"And if you wish to confirm that you don't have a principle in your body then you have some leading Conservatives campaigning for a No vote in a referendum or forming a coalition with Ukip.
"It is utterly preposterous and would be treated, rightly, with disillusion and derision, by ordinary members of the ordinary public...He is going to campaign for a Yes vote."
He added: "You would have me going bananas if I thought that David Cameron was contemplating campaigning for a No vote....
"There was never any intention to have a No vote. The idea was to settle our membership.
"There are limits to how far you can go ... to suddenly stand on your head and say 'I never meant it'".
He also said of his party leader: "I think he went for a referendum for the same reason that Harold Wilson did, party management."
Mr Cameron set out a pro-European view in the 'Bloomberg' speech in which he pledged an In/ Out referendum if he wins May's general election.
First Minister Nicola Sturgeon has demanded a "double lock" that would mean the UK could not leave the EU without agreement from every part of the UK, including Scotland.
But that call has been rejected by Mr Cameron.
London mayor Boris Johnson, widely tipped as a future Tory leader, yesterday predicted that the UK could leave the EU.
He forecast that there "would be a pretty testy, scratchy period (following an exit) ... (but) it wouldn't be disastrous."
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