Scotland's government began moves Friday to hold a new referendum on independence from the U.K. after the "Brexit" vote, saying it faced being taken out of the European Union against its will.
First Minister and Scottish National Party (SNP) leader Nicola Sturgeon said officials would plan for a "highly likely" vote on separation from the rest of the U.K.
Scots voted by 62 percent to 38 percent to remain in the EU, according to Friday's results, in contrast to the overall U.K.-wide result of 52 percent to 48 percent in favor of quitting the bloc.
A majority of voters in Northern Ireland also voted to remain in the EU, suggesting the U.K. faces internal constitutional upheaval as well as a contentious divorce from Brussels.
The issue is seen as important in Washington — and not just due to the historic "special relationship" with the U.K.; Scotland is currently home to 58 U.S. Trident II D-5 missiles, a key plank of NATO's nuclear deterrent.
Scotland's nationalist government wants to ban nuclear weapons on moral grounds within four years of gaining independence. This would force London to relocate the weapons to alternative bases in England or return the weapons to the U.S., costing billions of dollars and creating upheaval precisely at a time of heightened regional security concern.
The SNP, which won last month's Scottish Parliament election, pledged in its manifesto that there would be another ballot if there was a "significant and material" change in circumstances from the 2014 referendum in which Scots narrowly voted to remain in the U.K. by 55 percent to 45 percent.
A key argument in the 2014 poll was that Scotland's continued membership of the U.K. would also safeguard its future in the EU. A new vote could see a significant swing towards Scottish independence.
"We've got a united country in Scotland which wants to be part of Europe, and in the manifesto it said if Scotland was dragged out of Europe against the will of the Scottish people, then the Scottish Parliament should have the right to hold another independence referendum," said Sturgeon's predecessor, Alex Salmond.
His view was echoed by many in Scotland, including Harry Potter author J.K. Rowling who tweeted: "Scotland will seek independence now," adding that British Prime Minister David Cameron's legacy "will be breaking up two unions."
Cameron announced Friday that he was stepping down and would leave office by the fall.
However, a new independence campaign would face fresh headwinds; in particular, Scotland's oil-dependent economy has been severely dented by a collapse in global oil prices since the last referendum.
In addition, Scotland would likely have to join the Euro currency zone in order to re-enter the EU as an independent nation, raising the prospect of a cross-border currency divide within Britain even though two-thirds of Scotland's economic output is to the rest of the U.K.
The Obama administration has indicated that it would prefer Scotland and England to stay together — and for the U.K. to remain inside the EU, but Washington now faces a fractured transatlantic landscape.
Separation from the rest of Britain would end three centuries of shared history and would be the biggest constitutional upheaval since the Act of Union in 1707.
There could also be renewed questions about Northern Ireland's future. Irish nationalist party Sinn Fein, which opposes British rule in Northern Ireland, said the Brexit result showed that Britain's government "has forfeited any mandate to represent economic or political interests of people in Northern Ireland."