Voters should think of the Union and stay in the EU, David Cameron has signalled.
The Prime Minister suggested that Scottish independence should be a consideration during the European Union referendum.
His comments came as he set out his official demands for reform of the EU and almost immediately came under fire from both sides of the argument.
Within hours a number of senior European politicians had suggested the Tory leader would struggle to achieve his aims.
Meanwhile, Tory Eurosceptics accused him of a climbdown over migration.
In a major speech, Mr Cameron announced that he had proposed a four year ban on migrants accessing benefits to other European leaders.
But the Conservative manifesto said the party would "insist" on the measure said during membership renegotiations.
Mr Cameron's speech fired the starting gun on the next phase of the campaign.
Boris Johnson, the Tory mayor of London, swiftly predicted there could be "blood all over the carpet" in Brussels.
The SNP have suggested that a UK-wide vote to leave the EU could trigger a second independence referendum.
Asked if his EU poll could threatened “the very survival of the UK”, Mr Cameron said that independence was one of the "arguments" that would be made closer to the vote.
"Once this negotiation is completed (that) is what needs to happen," he said.
“ So that when people go to the polls they are in possession of as much information as possible.
“ What does it mean for Britain’s economic future? What does it mean for national security? What does it mean for the UK?
“All those questions will be relevant. But I’m absolutely sure that this is the right process – the renegotiation and a referendum."
He added that the renegotiation was “one in which we can succeed in and, if we do, it will be good for Britain and good for the European Union”.
Mr Cameron's four objectives include protection non-eurozone countries like the UK, an exemption from “ever closer union”; cuts in red tape and immigration measures.
The Prime Minister quoted DWP analysis which claimed that about 40 per cent of recent EU migrants, including children, are “supported by the UK benefits system”, at an average cost of around £6,000 per year.
FDuring his speech Mr Cameron appeared to make an offer to other European politicians to do a deal on the issue.
“I understand how difficult some of these welfare issues are for other member states and I am open to different ways of dealing with this issue,” he said.
Jean-Claude Juncker, the President of the European Commission, is meeting George Osborne in Brussels today to discuss the UK’s renegotiation.
Mr Juncker’s spokesman said there were some things in the UK’s proposals that were “highly problematic” including “direct discrimination between EU citizens”.
Martin Schulz, the European Parliament president, has said he has “strong doubts” about the legality of a four year ban.
Stephen Gethins, the SNP’s European Affairs spokesperson accused Mr Cameron of taking the UK closer to the EU exit door.
He added: “It is becoming increasingly clear that David Cameron is struggling to get the deal he needs to placate his party’s Eurosceptics. At the same time as losing friends and influence across Europe, the Prime Minister has failed to properly consult the Scottish Government, which flies in the face of the so-called respect agenda the Tories had promised.”
Experts protested that the figures were skewed in a number of ways, including that migrants tended to have more children.
The Institute of Directors said that Mr Cameron had "hit the right notes" with British firms.
But the Business Secretary Sajid Javid warned that many smaller UK businesses wanted to leave the EU.
Lord Lawson, who leads the Conservatives for Britain campaign, described the Prime Minister’s aims as “tiddlers”.
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