David Cameron warned that the Union between England and Scotland was at its most fragile for years because of a "coarse and casual nationalism" on both sides of the border.
He urged English voters not to blame Scots for government failures and blamed support for the Scottish National Party on disillusionment with Labour rather than support for independence.
Speaking in Edinburgh, the Tory leader mounted a passionate defence of the Act of Union which marked its 300th anniversary seven months ago.
Mr Cameron said: "The future of our Union is looking more fragile, more threatened, than at any time in recent history.
"The SNP now promises to deliver independence within 10 years. At the same time there are those in England who want the SNP to succeed, who would like to see the Union fracture.
"They seek to use grievances to foster a narrow English nationalism. We must confront and defeat the ugly stain of separatism seeping through the Union flag."